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Robotic renal surgery bests open partial nephrectomy
RAPN was associated with a 61% decrease in intraoperative complications and a 71% decrease in overall complications in the IRON study.
Alessandro Larcher, MD, of San Raffaele Hospital and the Urological Research Institute in Milan, presented results from IRON during a live poster session at the virtual annual congress of the European Association of Urology.
The IRON study was performed in nine high-volume centers and involved 3,468 patients with renal cell cancer. Patients were recruited if they had a localized renal cell mass (cT1-2) with no nodal involvement or metastases. There were 2,405 patients who underwent RAPN and 1,063 who underwent OPN.
Intraoperative complications occurred in 5.7% of patients who underwent RAPN and in 9.3% of those who underwent OPN. Overall complications occurred in 33% and 18%, respectively (P < .001 for both).
“The complication profile was invariably in favor of robot-assisted surgery,” Dr. Larcher observed.
Patients who underwent RAPN had less estimated median blood loss (150 mL vs. 180 mL, P < .001) as well as lower rates of hemorrhagic complications (6.4% vs. 9%, P < .01) and urinary leakage (0.8% vs. 4.6%, P < .01).
The operative time was longer with RAPN than with OPN, at a median of 150 minutes and 120 minutes, respectively (P < .001). However, patients remained in the hospital for less time with RAPN than with OPN, at a median of 4 days and 6 days, respectively (P < .01).
RAPN was associated with fewer surgical complications than OPN according to the Clavien-Dindo system. Grade 2 or higher complications occurred in 12% and 20% of patients, respectively (P < .001). Grade 3 or higher complications occurred in 4% and 6.1%, respectively (P < .001).
“The benefit with respect to the complication risk reduction in the case of robot-assisted surgery was not affected by the tumor complexity, by the dimension of the mass, the comorbidities of the patients, or the baseline renal function,” Dr. Larcher said. “[T]he advantage after robot-assisted surgery is consistent regardless of all these features.”
Early renal function was better after OPN, but there was no significant difference between the two groups at 1 year of follow-up. The median ischemia time was 15 minutes with OPN and 16 minutes with RAPN (P < .001).
Postoperatively, the median estimated glomerular filtration rate was 78 mL/min/1.73m2 with OPN and 76 mL/min/1.73m2 with RAPN (P < .001). At 1 year, the median estimated glomerular filtration rate was 68 and 71 mL/min/1.73m2, respectively (P = .5).
Dr. Larcher noted that there was no difference between RAPN and OPN in terms of 5-year oncologic outcomes. Local recurrence occurred in 1.6% and 2.1% of patients, respectively (P = .06); systemic progression was seen in 1.8% and 4.5%, respectively (P = .5); and clinical progression was observed in 3.2% and 6.6%, respectively (P = .9).
“[IRON is] a really powerful study. It’s one of those studies that kind of has to be done,” said Ben Challacombe, MBBS, a consultant urological surgeon at Guy’s Hospital and St. Thomas’ Hospital in London who chaired the poster session during which these findings were presented.
Dr. Challacombe, who specializes in the treatment of kidney and prostatic disease using robotic surgery, noted that about 75% of procedures in the United Kingdom are now being performed with robotic assistance and queried what percentage of procedures should still be done by open surgery.
“I would turn it,” Dr. Larcher said. “What is the percentage of surgeons that should use one technique or the other?” In the IRON study, as well as other studies, surgical expertise, training, and center volumes were important.
“What the data are telling us is that those who are really confident in robotic surgeries can achieve even better outcomes, also in very complex cases,” Dr. Larcher said. “I think it’s not any longer dependent on the tumor factors. The answer to the question is only determined by human factors.”
The IRON study was supported by a grant from Intuitive. Dr. Larcher declared no conflicts of interest. Dr. Challacombe did not present any disclosures.
SOURCE: Larcher A et al. EAU20, Abstract 30. Eur Urol Open Sci 2020;19(Suppl 2):e142.
RAPN was associated with a 61% decrease in intraoperative complications and a 71% decrease in overall complications in the IRON study.
Alessandro Larcher, MD, of San Raffaele Hospital and the Urological Research Institute in Milan, presented results from IRON during a live poster session at the virtual annual congress of the European Association of Urology.
The IRON study was performed in nine high-volume centers and involved 3,468 patients with renal cell cancer. Patients were recruited if they had a localized renal cell mass (cT1-2) with no nodal involvement or metastases. There were 2,405 patients who underwent RAPN and 1,063 who underwent OPN.
Intraoperative complications occurred in 5.7% of patients who underwent RAPN and in 9.3% of those who underwent OPN. Overall complications occurred in 33% and 18%, respectively (P < .001 for both).
“The complication profile was invariably in favor of robot-assisted surgery,” Dr. Larcher observed.
Patients who underwent RAPN had less estimated median blood loss (150 mL vs. 180 mL, P < .001) as well as lower rates of hemorrhagic complications (6.4% vs. 9%, P < .01) and urinary leakage (0.8% vs. 4.6%, P < .01).
The operative time was longer with RAPN than with OPN, at a median of 150 minutes and 120 minutes, respectively (P < .001). However, patients remained in the hospital for less time with RAPN than with OPN, at a median of 4 days and 6 days, respectively (P < .01).
RAPN was associated with fewer surgical complications than OPN according to the Clavien-Dindo system. Grade 2 or higher complications occurred in 12% and 20% of patients, respectively (P < .001). Grade 3 or higher complications occurred in 4% and 6.1%, respectively (P < .001).
“The benefit with respect to the complication risk reduction in the case of robot-assisted surgery was not affected by the tumor complexity, by the dimension of the mass, the comorbidities of the patients, or the baseline renal function,” Dr. Larcher said. “[T]he advantage after robot-assisted surgery is consistent regardless of all these features.”
Early renal function was better after OPN, but there was no significant difference between the two groups at 1 year of follow-up. The median ischemia time was 15 minutes with OPN and 16 minutes with RAPN (P < .001).
Postoperatively, the median estimated glomerular filtration rate was 78 mL/min/1.73m2 with OPN and 76 mL/min/1.73m2 with RAPN (P < .001). At 1 year, the median estimated glomerular filtration rate was 68 and 71 mL/min/1.73m2, respectively (P = .5).
Dr. Larcher noted that there was no difference between RAPN and OPN in terms of 5-year oncologic outcomes. Local recurrence occurred in 1.6% and 2.1% of patients, respectively (P = .06); systemic progression was seen in 1.8% and 4.5%, respectively (P = .5); and clinical progression was observed in 3.2% and 6.6%, respectively (P = .9).
“[IRON is] a really powerful study. It’s one of those studies that kind of has to be done,” said Ben Challacombe, MBBS, a consultant urological surgeon at Guy’s Hospital and St. Thomas’ Hospital in London who chaired the poster session during which these findings were presented.
Dr. Challacombe, who specializes in the treatment of kidney and prostatic disease using robotic surgery, noted that about 75% of procedures in the United Kingdom are now being performed with robotic assistance and queried what percentage of procedures should still be done by open surgery.
“I would turn it,” Dr. Larcher said. “What is the percentage of surgeons that should use one technique or the other?” In the IRON study, as well as other studies, surgical expertise, training, and center volumes were important.
“What the data are telling us is that those who are really confident in robotic surgeries can achieve even better outcomes, also in very complex cases,” Dr. Larcher said. “I think it’s not any longer dependent on the tumor factors. The answer to the question is only determined by human factors.”
The IRON study was supported by a grant from Intuitive. Dr. Larcher declared no conflicts of interest. Dr. Challacombe did not present any disclosures.
SOURCE: Larcher A et al. EAU20, Abstract 30. Eur Urol Open Sci 2020;19(Suppl 2):e142.
RAPN was associated with a 61% decrease in intraoperative complications and a 71% decrease in overall complications in the IRON study.
Alessandro Larcher, MD, of San Raffaele Hospital and the Urological Research Institute in Milan, presented results from IRON during a live poster session at the virtual annual congress of the European Association of Urology.
The IRON study was performed in nine high-volume centers and involved 3,468 patients with renal cell cancer. Patients were recruited if they had a localized renal cell mass (cT1-2) with no nodal involvement or metastases. There were 2,405 patients who underwent RAPN and 1,063 who underwent OPN.
Intraoperative complications occurred in 5.7% of patients who underwent RAPN and in 9.3% of those who underwent OPN. Overall complications occurred in 33% and 18%, respectively (P < .001 for both).
“The complication profile was invariably in favor of robot-assisted surgery,” Dr. Larcher observed.
Patients who underwent RAPN had less estimated median blood loss (150 mL vs. 180 mL, P < .001) as well as lower rates of hemorrhagic complications (6.4% vs. 9%, P < .01) and urinary leakage (0.8% vs. 4.6%, P < .01).
The operative time was longer with RAPN than with OPN, at a median of 150 minutes and 120 minutes, respectively (P < .001). However, patients remained in the hospital for less time with RAPN than with OPN, at a median of 4 days and 6 days, respectively (P < .01).
RAPN was associated with fewer surgical complications than OPN according to the Clavien-Dindo system. Grade 2 or higher complications occurred in 12% and 20% of patients, respectively (P < .001). Grade 3 or higher complications occurred in 4% and 6.1%, respectively (P < .001).
“The benefit with respect to the complication risk reduction in the case of robot-assisted surgery was not affected by the tumor complexity, by the dimension of the mass, the comorbidities of the patients, or the baseline renal function,” Dr. Larcher said. “[T]he advantage after robot-assisted surgery is consistent regardless of all these features.”
Early renal function was better after OPN, but there was no significant difference between the two groups at 1 year of follow-up. The median ischemia time was 15 minutes with OPN and 16 minutes with RAPN (P < .001).
Postoperatively, the median estimated glomerular filtration rate was 78 mL/min/1.73m2 with OPN and 76 mL/min/1.73m2 with RAPN (P < .001). At 1 year, the median estimated glomerular filtration rate was 68 and 71 mL/min/1.73m2, respectively (P = .5).
Dr. Larcher noted that there was no difference between RAPN and OPN in terms of 5-year oncologic outcomes. Local recurrence occurred in 1.6% and 2.1% of patients, respectively (P = .06); systemic progression was seen in 1.8% and 4.5%, respectively (P = .5); and clinical progression was observed in 3.2% and 6.6%, respectively (P = .9).
“[IRON is] a really powerful study. It’s one of those studies that kind of has to be done,” said Ben Challacombe, MBBS, a consultant urological surgeon at Guy’s Hospital and St. Thomas’ Hospital in London who chaired the poster session during which these findings were presented.
Dr. Challacombe, who specializes in the treatment of kidney and prostatic disease using robotic surgery, noted that about 75% of procedures in the United Kingdom are now being performed with robotic assistance and queried what percentage of procedures should still be done by open surgery.
“I would turn it,” Dr. Larcher said. “What is the percentage of surgeons that should use one technique or the other?” In the IRON study, as well as other studies, surgical expertise, training, and center volumes were important.
“What the data are telling us is that those who are really confident in robotic surgeries can achieve even better outcomes, also in very complex cases,” Dr. Larcher said. “I think it’s not any longer dependent on the tumor factors. The answer to the question is only determined by human factors.”
The IRON study was supported by a grant from Intuitive. Dr. Larcher declared no conflicts of interest. Dr. Challacombe did not present any disclosures.
SOURCE: Larcher A et al. EAU20, Abstract 30. Eur Urol Open Sci 2020;19(Suppl 2):e142.
FROM EAU20
Diary of a rheumatologist who briefly became a COVID hospitalist
When the coronavirus pandemic hit New York City in early March, the Hospital for Special Surgery leadership decided that the best way to serve the city was to stop elective orthopedic procedures temporarily and use the facility to take on patients from its sister institution, NewYork–Presbyterian Hospital.
As in other institutions, it was all hands on deck. , other internal medicine subspecialists were asked to volunteer, including rheumatologists and primary care sports medicine doctors.
As a rheumatologist, it had been well over 10 years since I had last done any inpatient work. I was filled with trepidation, but I was also excited to dive in.
April 4:
Feeling very unmoored. I am in unfamiliar territory, and it’s terrifying. There are so many things that I no longer know how to do. Thankfully, the hospitalists are gracious, extremely supportive, and helpful.
My N95 doesn’t fit well. It’s never fit — not during residency or fellowship, not in any job I’ve had, and not today. The lady fit-testing me said she was sorry, but the look on her face said, “I’m sorry, but you’re going to die.”
April 7:
We don’t know how to treat coronavirus. I’ve sent some patients home, others I’ve sent to the ICU. Thank goodness for treatment algorithms from leadership, but we are sorely lacking good-quality data.
Our infectious disease doctor doesn’t think hydroxychloroquine works at all; I suspect he is right. The guidance right now is to give hydroxychloroquine and azithromycin to everyone who is sick enough to be admitted, but there are methodologic flaws in the early enthusiastic preprints, and so far, I’ve not noticed any demonstrable benefit.
The only thing that seems to be happening is that I am seeing more QT prolongation — not something I previously counseled my rheumatology patients on.
April 9:
The patients have been, with a few exceptions, alone in the room. They’re not allowed to have visitors and are required to wear masks all the time. Anyone who enters their rooms is fully covered up so you can barely see them. It’s anonymous and dehumanizing.
We’re instructed to take histories by phone in order to limit the time spent in each room. I buck this instruction; I still take histories in person because human contact seems more important now than ever.
Except maybe I should be smarter about this. One of my patients refuses any treatment, including oxygen support. She firmly believes this is a result of 5G networks — something I later discovered was a common conspiracy theory. She refused to wear a mask despite having a very bad cough. She coughed in my face a lot when we were chatting. My face with my ill-fitting N95 mask. Maybe the fit-testing lady’s eyes weren’t lying and I will die after all.
April 15:
On the days when I’m not working as a hospitalist, I am still doing remote visits with my rheumatology patients. It feels good to be doing something familiar and something I’m actually good at. But it is surreal to be faced with the quotidian on one hand and life and death on the other.
I recently saw a fairly new patient, and I still haven’t figured out if she has a rheumatic condition or if her symptoms all stem from an alcohol use disorder. In our previous visits, she could barely acknowledge that her drinking was an issue. On today’s visit, she told me she was 1½ months sober.
I don’t know her very well, but it was the happiest news I’d heard in a long time. I was so beside myself with joy that I cried, which says more about my current emotional state than anything else, really.
April 21:
On my panel of patients, I have three women with COVID-19 — all of whom lost their husbands to COVID-19, and none of whom were able to say their goodbyes. I cannot even begin to imagine what it must be like to survive this period of illness, isolation, and fear, only to be met on the other side by grief.
Rheumatology doesn’t lend itself too well to such existential concerns; I am not equipped for this. Perhaps my only advantage as a rheumatologist is that I know how to use IVIG, anakinra, and tocilizumab.
Someone on my panel was started on anakinra, and it turned his case around. Would he have gotten better without it anyway? We’ll never know for sure.
April 28:
Patients seem to be requiring prolonged intubation. We have now reached the stage where patients are alive but trached and PEGed. One of my patients had been intubated for close to 3 weeks. She was one of four people in her family who contracted the illness (they had had a dinner party before New York’s state of emergency was declared). We thought she might die once she was extubated, but she is still fighting. Unconscious, unarousable, but breathing on her own.
Will she ever wake up? We don’t know. We put the onus on her family to make decisions about placing a PEG tube in. They can only do so from a distance with imperfect information gleaned from periodic, brief FaceTime interactions — where no interaction happens at all.
May 4:
It’s my last day as a “COVID hospitalist.” When I first started, I felt like I was being helpful. Walking home in the middle of the 7 PM cheers for healthcare workers frequently left me teary eyed. As horrible as the situation was, I was proud of myself for volunteering to help and appreciative of a broken city’s gratitude toward all healthcare workers in general. Maybe I bought into the idea that, like many others around me, I am a hero.
I don’t feel like a hero, though. The stuff I saw was easy compared with the stuff that my colleagues in critical care saw. Our hospital accepted the more stable patient transfers from our sister hospitals. Patients who remained in the NewYork–Presbyterian system were sicker, with encephalitis, thrombotic complications, multiorgan failure, and cytokine release syndrome. It’s the doctors who took care of those patients who deserve to be called heroes.
No, I am no hero. But did my volunteering make a difference? It made a difference to me. The overwhelming feeling I am left with isn’t pride; it’s humility. I feel humbled that I could feel so unexpectedly touched by the lives of people that I had no idea I could feel touched by.
Postscript:
My patient Esther [name changed to hide her identity] died from COVID-19. She was MY patient — not a patient I met as a COVID hospitalist, but a patient with rheumatoid arthritis whom I cared for for years.
She had scleromalacia and multiple failed scleral grafts, which made her profoundly sad. She fought her anxiety fiercely and always with poise and panache. One way she dealt with her anxiety was that she constantly messaged me via our EHR portal. She ran everything by me and trusted me to be her rock.
The past month has been so busy that I just now noticed it had been a month since I last heard from her. I tried to call her but got her voicemail. It wasn’t until I exchanged messages with her ophthalmologist that I found out she had passed away from complications of COVID-19.
She was taking rituximab and mycophenolate. I wonder if these drugs made her sicker than she would have been otherwise; it fills me with sadness. I wonder if she was alone like my other COVID-19 patients. I wonder if she was afraid. I am sorry that I wasn’t able to say goodbye.
Karmela Kim Chan, MD, is an assistant professor at Weill Cornell Medical College and an attending physician at Hospital for Special Surgery and Memorial Sloan Kettering Cancer Center in New York City. Before moving to New York City, she spent 7 years in private practice in Rhode Island and was a columnist for this rheumatology publication, writing about the challenges of starting life as a full-fledged rheumatologist in a private practice.
A version of this article originally appeared on Medscape.com. This article is part of a partnership between Medscape and Hospital for Special Surgery.
When the coronavirus pandemic hit New York City in early March, the Hospital for Special Surgery leadership decided that the best way to serve the city was to stop elective orthopedic procedures temporarily and use the facility to take on patients from its sister institution, NewYork–Presbyterian Hospital.
As in other institutions, it was all hands on deck. , other internal medicine subspecialists were asked to volunteer, including rheumatologists and primary care sports medicine doctors.
As a rheumatologist, it had been well over 10 years since I had last done any inpatient work. I was filled with trepidation, but I was also excited to dive in.
April 4:
Feeling very unmoored. I am in unfamiliar territory, and it’s terrifying. There are so many things that I no longer know how to do. Thankfully, the hospitalists are gracious, extremely supportive, and helpful.
My N95 doesn’t fit well. It’s never fit — not during residency or fellowship, not in any job I’ve had, and not today. The lady fit-testing me said she was sorry, but the look on her face said, “I’m sorry, but you’re going to die.”
April 7:
We don’t know how to treat coronavirus. I’ve sent some patients home, others I’ve sent to the ICU. Thank goodness for treatment algorithms from leadership, but we are sorely lacking good-quality data.
Our infectious disease doctor doesn’t think hydroxychloroquine works at all; I suspect he is right. The guidance right now is to give hydroxychloroquine and azithromycin to everyone who is sick enough to be admitted, but there are methodologic flaws in the early enthusiastic preprints, and so far, I’ve not noticed any demonstrable benefit.
The only thing that seems to be happening is that I am seeing more QT prolongation — not something I previously counseled my rheumatology patients on.
April 9:
The patients have been, with a few exceptions, alone in the room. They’re not allowed to have visitors and are required to wear masks all the time. Anyone who enters their rooms is fully covered up so you can barely see them. It’s anonymous and dehumanizing.
We’re instructed to take histories by phone in order to limit the time spent in each room. I buck this instruction; I still take histories in person because human contact seems more important now than ever.
Except maybe I should be smarter about this. One of my patients refuses any treatment, including oxygen support. She firmly believes this is a result of 5G networks — something I later discovered was a common conspiracy theory. She refused to wear a mask despite having a very bad cough. She coughed in my face a lot when we were chatting. My face with my ill-fitting N95 mask. Maybe the fit-testing lady’s eyes weren’t lying and I will die after all.
April 15:
On the days when I’m not working as a hospitalist, I am still doing remote visits with my rheumatology patients. It feels good to be doing something familiar and something I’m actually good at. But it is surreal to be faced with the quotidian on one hand and life and death on the other.
I recently saw a fairly new patient, and I still haven’t figured out if she has a rheumatic condition or if her symptoms all stem from an alcohol use disorder. In our previous visits, she could barely acknowledge that her drinking was an issue. On today’s visit, she told me she was 1½ months sober.
I don’t know her very well, but it was the happiest news I’d heard in a long time. I was so beside myself with joy that I cried, which says more about my current emotional state than anything else, really.
April 21:
On my panel of patients, I have three women with COVID-19 — all of whom lost their husbands to COVID-19, and none of whom were able to say their goodbyes. I cannot even begin to imagine what it must be like to survive this period of illness, isolation, and fear, only to be met on the other side by grief.
Rheumatology doesn’t lend itself too well to such existential concerns; I am not equipped for this. Perhaps my only advantage as a rheumatologist is that I know how to use IVIG, anakinra, and tocilizumab.
Someone on my panel was started on anakinra, and it turned his case around. Would he have gotten better without it anyway? We’ll never know for sure.
April 28:
Patients seem to be requiring prolonged intubation. We have now reached the stage where patients are alive but trached and PEGed. One of my patients had been intubated for close to 3 weeks. She was one of four people in her family who contracted the illness (they had had a dinner party before New York’s state of emergency was declared). We thought she might die once she was extubated, but she is still fighting. Unconscious, unarousable, but breathing on her own.
Will she ever wake up? We don’t know. We put the onus on her family to make decisions about placing a PEG tube in. They can only do so from a distance with imperfect information gleaned from periodic, brief FaceTime interactions — where no interaction happens at all.
May 4:
It’s my last day as a “COVID hospitalist.” When I first started, I felt like I was being helpful. Walking home in the middle of the 7 PM cheers for healthcare workers frequently left me teary eyed. As horrible as the situation was, I was proud of myself for volunteering to help and appreciative of a broken city’s gratitude toward all healthcare workers in general. Maybe I bought into the idea that, like many others around me, I am a hero.
I don’t feel like a hero, though. The stuff I saw was easy compared with the stuff that my colleagues in critical care saw. Our hospital accepted the more stable patient transfers from our sister hospitals. Patients who remained in the NewYork–Presbyterian system were sicker, with encephalitis, thrombotic complications, multiorgan failure, and cytokine release syndrome. It’s the doctors who took care of those patients who deserve to be called heroes.
No, I am no hero. But did my volunteering make a difference? It made a difference to me. The overwhelming feeling I am left with isn’t pride; it’s humility. I feel humbled that I could feel so unexpectedly touched by the lives of people that I had no idea I could feel touched by.
Postscript:
My patient Esther [name changed to hide her identity] died from COVID-19. She was MY patient — not a patient I met as a COVID hospitalist, but a patient with rheumatoid arthritis whom I cared for for years.
She had scleromalacia and multiple failed scleral grafts, which made her profoundly sad. She fought her anxiety fiercely and always with poise and panache. One way she dealt with her anxiety was that she constantly messaged me via our EHR portal. She ran everything by me and trusted me to be her rock.
The past month has been so busy that I just now noticed it had been a month since I last heard from her. I tried to call her but got her voicemail. It wasn’t until I exchanged messages with her ophthalmologist that I found out she had passed away from complications of COVID-19.
She was taking rituximab and mycophenolate. I wonder if these drugs made her sicker than she would have been otherwise; it fills me with sadness. I wonder if she was alone like my other COVID-19 patients. I wonder if she was afraid. I am sorry that I wasn’t able to say goodbye.
Karmela Kim Chan, MD, is an assistant professor at Weill Cornell Medical College and an attending physician at Hospital for Special Surgery and Memorial Sloan Kettering Cancer Center in New York City. Before moving to New York City, she spent 7 years in private practice in Rhode Island and was a columnist for this rheumatology publication, writing about the challenges of starting life as a full-fledged rheumatologist in a private practice.
A version of this article originally appeared on Medscape.com. This article is part of a partnership between Medscape and Hospital for Special Surgery.
When the coronavirus pandemic hit New York City in early March, the Hospital for Special Surgery leadership decided that the best way to serve the city was to stop elective orthopedic procedures temporarily and use the facility to take on patients from its sister institution, NewYork–Presbyterian Hospital.
As in other institutions, it was all hands on deck. , other internal medicine subspecialists were asked to volunteer, including rheumatologists and primary care sports medicine doctors.
As a rheumatologist, it had been well over 10 years since I had last done any inpatient work. I was filled with trepidation, but I was also excited to dive in.
April 4:
Feeling very unmoored. I am in unfamiliar territory, and it’s terrifying. There are so many things that I no longer know how to do. Thankfully, the hospitalists are gracious, extremely supportive, and helpful.
My N95 doesn’t fit well. It’s never fit — not during residency or fellowship, not in any job I’ve had, and not today. The lady fit-testing me said she was sorry, but the look on her face said, “I’m sorry, but you’re going to die.”
April 7:
We don’t know how to treat coronavirus. I’ve sent some patients home, others I’ve sent to the ICU. Thank goodness for treatment algorithms from leadership, but we are sorely lacking good-quality data.
Our infectious disease doctor doesn’t think hydroxychloroquine works at all; I suspect he is right. The guidance right now is to give hydroxychloroquine and azithromycin to everyone who is sick enough to be admitted, but there are methodologic flaws in the early enthusiastic preprints, and so far, I’ve not noticed any demonstrable benefit.
The only thing that seems to be happening is that I am seeing more QT prolongation — not something I previously counseled my rheumatology patients on.
April 9:
The patients have been, with a few exceptions, alone in the room. They’re not allowed to have visitors and are required to wear masks all the time. Anyone who enters their rooms is fully covered up so you can barely see them. It’s anonymous and dehumanizing.
We’re instructed to take histories by phone in order to limit the time spent in each room. I buck this instruction; I still take histories in person because human contact seems more important now than ever.
Except maybe I should be smarter about this. One of my patients refuses any treatment, including oxygen support. She firmly believes this is a result of 5G networks — something I later discovered was a common conspiracy theory. She refused to wear a mask despite having a very bad cough. She coughed in my face a lot when we were chatting. My face with my ill-fitting N95 mask. Maybe the fit-testing lady’s eyes weren’t lying and I will die after all.
April 15:
On the days when I’m not working as a hospitalist, I am still doing remote visits with my rheumatology patients. It feels good to be doing something familiar and something I’m actually good at. But it is surreal to be faced with the quotidian on one hand and life and death on the other.
I recently saw a fairly new patient, and I still haven’t figured out if she has a rheumatic condition or if her symptoms all stem from an alcohol use disorder. In our previous visits, she could barely acknowledge that her drinking was an issue. On today’s visit, she told me she was 1½ months sober.
I don’t know her very well, but it was the happiest news I’d heard in a long time. I was so beside myself with joy that I cried, which says more about my current emotional state than anything else, really.
April 21:
On my panel of patients, I have three women with COVID-19 — all of whom lost their husbands to COVID-19, and none of whom were able to say their goodbyes. I cannot even begin to imagine what it must be like to survive this period of illness, isolation, and fear, only to be met on the other side by grief.
Rheumatology doesn’t lend itself too well to such existential concerns; I am not equipped for this. Perhaps my only advantage as a rheumatologist is that I know how to use IVIG, anakinra, and tocilizumab.
Someone on my panel was started on anakinra, and it turned his case around. Would he have gotten better without it anyway? We’ll never know for sure.
April 28:
Patients seem to be requiring prolonged intubation. We have now reached the stage where patients are alive but trached and PEGed. One of my patients had been intubated for close to 3 weeks. She was one of four people in her family who contracted the illness (they had had a dinner party before New York’s state of emergency was declared). We thought she might die once she was extubated, but she is still fighting. Unconscious, unarousable, but breathing on her own.
Will she ever wake up? We don’t know. We put the onus on her family to make decisions about placing a PEG tube in. They can only do so from a distance with imperfect information gleaned from periodic, brief FaceTime interactions — where no interaction happens at all.
May 4:
It’s my last day as a “COVID hospitalist.” When I first started, I felt like I was being helpful. Walking home in the middle of the 7 PM cheers for healthcare workers frequently left me teary eyed. As horrible as the situation was, I was proud of myself for volunteering to help and appreciative of a broken city’s gratitude toward all healthcare workers in general. Maybe I bought into the idea that, like many others around me, I am a hero.
I don’t feel like a hero, though. The stuff I saw was easy compared with the stuff that my colleagues in critical care saw. Our hospital accepted the more stable patient transfers from our sister hospitals. Patients who remained in the NewYork–Presbyterian system were sicker, with encephalitis, thrombotic complications, multiorgan failure, and cytokine release syndrome. It’s the doctors who took care of those patients who deserve to be called heroes.
No, I am no hero. But did my volunteering make a difference? It made a difference to me. The overwhelming feeling I am left with isn’t pride; it’s humility. I feel humbled that I could feel so unexpectedly touched by the lives of people that I had no idea I could feel touched by.
Postscript:
My patient Esther [name changed to hide her identity] died from COVID-19. She was MY patient — not a patient I met as a COVID hospitalist, but a patient with rheumatoid arthritis whom I cared for for years.
She had scleromalacia and multiple failed scleral grafts, which made her profoundly sad. She fought her anxiety fiercely and always with poise and panache. One way she dealt with her anxiety was that she constantly messaged me via our EHR portal. She ran everything by me and trusted me to be her rock.
The past month has been so busy that I just now noticed it had been a month since I last heard from her. I tried to call her but got her voicemail. It wasn’t until I exchanged messages with her ophthalmologist that I found out she had passed away from complications of COVID-19.
She was taking rituximab and mycophenolate. I wonder if these drugs made her sicker than she would have been otherwise; it fills me with sadness. I wonder if she was alone like my other COVID-19 patients. I wonder if she was afraid. I am sorry that I wasn’t able to say goodbye.
Karmela Kim Chan, MD, is an assistant professor at Weill Cornell Medical College and an attending physician at Hospital for Special Surgery and Memorial Sloan Kettering Cancer Center in New York City. Before moving to New York City, she spent 7 years in private practice in Rhode Island and was a columnist for this rheumatology publication, writing about the challenges of starting life as a full-fledged rheumatologist in a private practice.
A version of this article originally appeared on Medscape.com. This article is part of a partnership between Medscape and Hospital for Special Surgery.
E.U. gives thumbs up for belantamab in R/R multiple myeloma
The first-in-class drug belantamab mafodotin (Blenrep, GlaxoSmithKline) has been recommended for conditional marketing approval in the European Union (EU) for use in the treatment of relapsed and refractory multiple myeloma in patients who have already tried other therapies.
The product was accepted into the European Medicines Agency (EMA) PRIME program for medicines that have potential to address unmet medical needs, the agency noted.
Belantamab mafodotin was also recently recommended for U.S. approval when a Food and Drug Administration advisory committee voted 12-0 in favor of the drug’s benefits outweighing risks in this patient population.
Specifically, these patients with refractory or relapsed multiple myeloma should have already tried treatment with one of the three major classes of drugs, namely an immunomodulatory agent, a proteasome inhibitor, and a CD-38 monoclonal antibody.
For patients who no longer respond to these drugs, the outlook is bleak, the EMA said. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed 3 months or less.
Belantamab mafodotin has a novel mechanism of action: It targets B-cell maturation antigen (BCMA), a protein present on the surface of virtually all multiple myeloma cells, but is absent from normal B-cells, thus “making it an ideal drug target,” the agency remarked.
The product is an antibody–drug conjugate that combines a monoclonal antibody that targets BCMA with the cytotoxic agent maleimidocaproyl monomethylauristatin F (mcMMAF). It homes in on BCMA on myeloma cell surfaces, and once inside the myeloma cell, the cytotoxic agent is released leading to apoptosis, the “programmed” death of the cancerous plasma cells, the agency explained.
Results from open-label study
The recommendation for conditional marketing authorization comes from the EMA Committee for Medicinal Products for Human Use (CHMP) and was based on a phase 2, open-label, randomized, two-arm study, DREAMM-2.
The study investigated the efficacy and safety of two doses of belantamab mafodotin in patients with multiple myeloma who still had active disease after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody.
Six-month results were published in December in The Lancet Oncology. The overall response rate was 31% in the cohort given a 2.5-mg/kg dose of the drug; 30 of 97 patients had outcomes that met the study’s positive threshold.
Another 99 patients in DREAMM-2 received a dose of 3.4 mg/kg, which was judged to have a less favorable safety profile.
The EMA has requested further clinical data, including final results from the phase 2 study, as well as results from a confirmatory phase 3 trial comparing belantamab mafodotin with pomalidomide plus low-dose dexamethasone (a standard treatment option for relapsed and refractory multiple myeloma).
Ocular toxicity
One of the most common side effects of the new drug experienced by participants in clinical trials was keratopathy, which affects the cornea. This ocular toxicity was seen at both drug doses.
The EMA noted that patients taking the drug would need to undergo specific ophthalmic examinations so that any findings can be promptly and adequately managed. As for all medicines, a risk management plan (RMP) will ensure rigorous safety monitoring of the medicine once authorized across the European Union, it added.
At the FDA advisory committee meeting, it was noted that 44% of patients in the group that received the 2.5-mg/kg dose experienced at least one episode of severe keratopathy. In some patients, the ocular side effects caused severe vision loss that interfered with patients’ activities of daily living, such as driving and reading, FDA staff said.
For the United States, the manufacturer proposed a risk evaluation and mitigation strategy (REMS) for the detection and treatment of potential complications of belantamab. This includes recommendations for ophthalmic examinations, including assessment of best corrected visual acuity prior to each treatment cycle and promptly for patients with worsening symptoms.
One of the FDA advisory committee panelists, Gita Thanarajasingam, MD, assistant professor of medicine at the Mayo Clinic, in Rochester, Minn., said belantamab appeared to be well tolerated with the exception of ocular toxicity. Physicians need to acknowledge how severe this risk may be for patients while keeping in mind that belantamab still may be more tolerable for some than current treatments, she said.
“It’s reasonable to leave open the option for decision-making. Patients can express their values and preferences,” Thanarajasingam said. “There’s adequate, albeit not complete, information to guide this risk–benefit discussion in a REMS program.”
Heidi D. Klepin, MD, a professor at Wake Forest University Health Sciences, Winston Salem, N.C., agreed that the informed consent process should allow patients “to choose whether the trade-off is worth it” with belantamab.
This article first appeared on Medscape.com.
The first-in-class drug belantamab mafodotin (Blenrep, GlaxoSmithKline) has been recommended for conditional marketing approval in the European Union (EU) for use in the treatment of relapsed and refractory multiple myeloma in patients who have already tried other therapies.
The product was accepted into the European Medicines Agency (EMA) PRIME program for medicines that have potential to address unmet medical needs, the agency noted.
Belantamab mafodotin was also recently recommended for U.S. approval when a Food and Drug Administration advisory committee voted 12-0 in favor of the drug’s benefits outweighing risks in this patient population.
Specifically, these patients with refractory or relapsed multiple myeloma should have already tried treatment with one of the three major classes of drugs, namely an immunomodulatory agent, a proteasome inhibitor, and a CD-38 monoclonal antibody.
For patients who no longer respond to these drugs, the outlook is bleak, the EMA said. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed 3 months or less.
Belantamab mafodotin has a novel mechanism of action: It targets B-cell maturation antigen (BCMA), a protein present on the surface of virtually all multiple myeloma cells, but is absent from normal B-cells, thus “making it an ideal drug target,” the agency remarked.
The product is an antibody–drug conjugate that combines a monoclonal antibody that targets BCMA with the cytotoxic agent maleimidocaproyl monomethylauristatin F (mcMMAF). It homes in on BCMA on myeloma cell surfaces, and once inside the myeloma cell, the cytotoxic agent is released leading to apoptosis, the “programmed” death of the cancerous plasma cells, the agency explained.
Results from open-label study
The recommendation for conditional marketing authorization comes from the EMA Committee for Medicinal Products for Human Use (CHMP) and was based on a phase 2, open-label, randomized, two-arm study, DREAMM-2.
The study investigated the efficacy and safety of two doses of belantamab mafodotin in patients with multiple myeloma who still had active disease after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody.
Six-month results were published in December in The Lancet Oncology. The overall response rate was 31% in the cohort given a 2.5-mg/kg dose of the drug; 30 of 97 patients had outcomes that met the study’s positive threshold.
Another 99 patients in DREAMM-2 received a dose of 3.4 mg/kg, which was judged to have a less favorable safety profile.
The EMA has requested further clinical data, including final results from the phase 2 study, as well as results from a confirmatory phase 3 trial comparing belantamab mafodotin with pomalidomide plus low-dose dexamethasone (a standard treatment option for relapsed and refractory multiple myeloma).
Ocular toxicity
One of the most common side effects of the new drug experienced by participants in clinical trials was keratopathy, which affects the cornea. This ocular toxicity was seen at both drug doses.
The EMA noted that patients taking the drug would need to undergo specific ophthalmic examinations so that any findings can be promptly and adequately managed. As for all medicines, a risk management plan (RMP) will ensure rigorous safety monitoring of the medicine once authorized across the European Union, it added.
At the FDA advisory committee meeting, it was noted that 44% of patients in the group that received the 2.5-mg/kg dose experienced at least one episode of severe keratopathy. In some patients, the ocular side effects caused severe vision loss that interfered with patients’ activities of daily living, such as driving and reading, FDA staff said.
For the United States, the manufacturer proposed a risk evaluation and mitigation strategy (REMS) for the detection and treatment of potential complications of belantamab. This includes recommendations for ophthalmic examinations, including assessment of best corrected visual acuity prior to each treatment cycle and promptly for patients with worsening symptoms.
One of the FDA advisory committee panelists, Gita Thanarajasingam, MD, assistant professor of medicine at the Mayo Clinic, in Rochester, Minn., said belantamab appeared to be well tolerated with the exception of ocular toxicity. Physicians need to acknowledge how severe this risk may be for patients while keeping in mind that belantamab still may be more tolerable for some than current treatments, she said.
“It’s reasonable to leave open the option for decision-making. Patients can express their values and preferences,” Thanarajasingam said. “There’s adequate, albeit not complete, information to guide this risk–benefit discussion in a REMS program.”
Heidi D. Klepin, MD, a professor at Wake Forest University Health Sciences, Winston Salem, N.C., agreed that the informed consent process should allow patients “to choose whether the trade-off is worth it” with belantamab.
This article first appeared on Medscape.com.
The first-in-class drug belantamab mafodotin (Blenrep, GlaxoSmithKline) has been recommended for conditional marketing approval in the European Union (EU) for use in the treatment of relapsed and refractory multiple myeloma in patients who have already tried other therapies.
The product was accepted into the European Medicines Agency (EMA) PRIME program for medicines that have potential to address unmet medical needs, the agency noted.
Belantamab mafodotin was also recently recommended for U.S. approval when a Food and Drug Administration advisory committee voted 12-0 in favor of the drug’s benefits outweighing risks in this patient population.
Specifically, these patients with refractory or relapsed multiple myeloma should have already tried treatment with one of the three major classes of drugs, namely an immunomodulatory agent, a proteasome inhibitor, and a CD-38 monoclonal antibody.
For patients who no longer respond to these drugs, the outlook is bleak, the EMA said. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed 3 months or less.
Belantamab mafodotin has a novel mechanism of action: It targets B-cell maturation antigen (BCMA), a protein present on the surface of virtually all multiple myeloma cells, but is absent from normal B-cells, thus “making it an ideal drug target,” the agency remarked.
The product is an antibody–drug conjugate that combines a monoclonal antibody that targets BCMA with the cytotoxic agent maleimidocaproyl monomethylauristatin F (mcMMAF). It homes in on BCMA on myeloma cell surfaces, and once inside the myeloma cell, the cytotoxic agent is released leading to apoptosis, the “programmed” death of the cancerous plasma cells, the agency explained.
Results from open-label study
The recommendation for conditional marketing authorization comes from the EMA Committee for Medicinal Products for Human Use (CHMP) and was based on a phase 2, open-label, randomized, two-arm study, DREAMM-2.
The study investigated the efficacy and safety of two doses of belantamab mafodotin in patients with multiple myeloma who still had active disease after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody.
Six-month results were published in December in The Lancet Oncology. The overall response rate was 31% in the cohort given a 2.5-mg/kg dose of the drug; 30 of 97 patients had outcomes that met the study’s positive threshold.
Another 99 patients in DREAMM-2 received a dose of 3.4 mg/kg, which was judged to have a less favorable safety profile.
The EMA has requested further clinical data, including final results from the phase 2 study, as well as results from a confirmatory phase 3 trial comparing belantamab mafodotin with pomalidomide plus low-dose dexamethasone (a standard treatment option for relapsed and refractory multiple myeloma).
Ocular toxicity
One of the most common side effects of the new drug experienced by participants in clinical trials was keratopathy, which affects the cornea. This ocular toxicity was seen at both drug doses.
The EMA noted that patients taking the drug would need to undergo specific ophthalmic examinations so that any findings can be promptly and adequately managed. As for all medicines, a risk management plan (RMP) will ensure rigorous safety monitoring of the medicine once authorized across the European Union, it added.
At the FDA advisory committee meeting, it was noted that 44% of patients in the group that received the 2.5-mg/kg dose experienced at least one episode of severe keratopathy. In some patients, the ocular side effects caused severe vision loss that interfered with patients’ activities of daily living, such as driving and reading, FDA staff said.
For the United States, the manufacturer proposed a risk evaluation and mitigation strategy (REMS) for the detection and treatment of potential complications of belantamab. This includes recommendations for ophthalmic examinations, including assessment of best corrected visual acuity prior to each treatment cycle and promptly for patients with worsening symptoms.
One of the FDA advisory committee panelists, Gita Thanarajasingam, MD, assistant professor of medicine at the Mayo Clinic, in Rochester, Minn., said belantamab appeared to be well tolerated with the exception of ocular toxicity. Physicians need to acknowledge how severe this risk may be for patients while keeping in mind that belantamab still may be more tolerable for some than current treatments, she said.
“It’s reasonable to leave open the option for decision-making. Patients can express their values and preferences,” Thanarajasingam said. “There’s adequate, albeit not complete, information to guide this risk–benefit discussion in a REMS program.”
Heidi D. Klepin, MD, a professor at Wake Forest University Health Sciences, Winston Salem, N.C., agreed that the informed consent process should allow patients “to choose whether the trade-off is worth it” with belantamab.
This article first appeared on Medscape.com.
New realities
Dear colleagues,
The August issue of The New Gastroenterologist has arrived! The summer of 2020 certainly looks different from years past, as the COVID-19 pandemic rages on and we continue to adjust to the new realities of our personal and professional lives. Our third-year fellows have graduated amidst these unusual circumstances, some facing an uncertain job landscape. Yet their hard work is not lost upon us – as we must step back to recognize their achievements and bid them congratulations on the culmination of several years of training.
The pandemic has been pervasive in medical education with a profound effect on our training programs. Two very resourceful fellows, Indira Bhavsar-Burke and Claire Jansson-Knodell (Indiana University), share their experience with COVID-19 and how they used this time to create an online curriculum for medical students who were pulled from their gastroenterology clinical rotations.
As we remain socially distanced, connecting through virtual platforms and social media seems more important than ever, but digital media can be difficult to navigate as physicians. Austin Chiang (Thomas Jefferson University) offers a candid snapshot of the benefits and pitfalls of social media as a gastroenterologist, with advice on how to optimize one’s professional presence online.
This quarter’s “In Focus” feature is an excellent, high-yield review of eosinophilic esophagitis. Ronak Vashi Patel and Ikuo Hirano (Northwestern University) seek to answer frequently asked questions about diagnostic considerations and the approach to management by reviewing therapeutic options – a truly valuable clinical piece to guide any young gastroenterologist.
Our medical ethics series features a poignant piece written by Diana Anderson (University of California, San Francisco) and David Seres (Columbia University) on the role of nutritional support in patients with restrictive eating disorders. The article addresses the complex interplay between certain diagnoses and our emotive response as clinicians – a critical piece of patient care that is seldom discussed. The authors implore us to consider this difficult question: Could our unconscious partiality as physicians be worse than intentional harm?
Adjoa Anyane-Yeboa (Harvard University) discusses how her interest in health equity and health care policy led her to the Commonwealth Fund Fellowship in Minority Health Policy. Her passion for health care delivery reform and the care of vulnerable populations shines through as she describes how this post-GI fellowship pathway has been formative in shaping her career as a dynamic new gastroenterologist.
For those interested in serving as an expert witness, seasoned malpractice attorneys Daniel Mills and Courtney Lindbert (Cunningham, Meyer & Vedrine P.C.) offer a salient list of the “do’s and don’ts” of the medical expert. Finally, this summer’s DHPA Private Practice Perspectives article, written by Michael Weinstein (Capital Digestive Care), offers important considerations for evaluating independent GI practices and how their response to COVID-19 can dictate their preparedness for future crises.
If you have interest in contributing or have ideas for future TNG topics, please contact me ([email protected]), or Ryan Farrell ([email protected]), managing editor of TNG.
Stay well,
Vijaya L. Rao, MD
Editor-in-Chief
Assistant professor of medicine, University of Chicago, section of gastroenterology, hepatology & nutrition
Dear colleagues,
The August issue of The New Gastroenterologist has arrived! The summer of 2020 certainly looks different from years past, as the COVID-19 pandemic rages on and we continue to adjust to the new realities of our personal and professional lives. Our third-year fellows have graduated amidst these unusual circumstances, some facing an uncertain job landscape. Yet their hard work is not lost upon us – as we must step back to recognize their achievements and bid them congratulations on the culmination of several years of training.
The pandemic has been pervasive in medical education with a profound effect on our training programs. Two very resourceful fellows, Indira Bhavsar-Burke and Claire Jansson-Knodell (Indiana University), share their experience with COVID-19 and how they used this time to create an online curriculum for medical students who were pulled from their gastroenterology clinical rotations.
As we remain socially distanced, connecting through virtual platforms and social media seems more important than ever, but digital media can be difficult to navigate as physicians. Austin Chiang (Thomas Jefferson University) offers a candid snapshot of the benefits and pitfalls of social media as a gastroenterologist, with advice on how to optimize one’s professional presence online.
This quarter’s “In Focus” feature is an excellent, high-yield review of eosinophilic esophagitis. Ronak Vashi Patel and Ikuo Hirano (Northwestern University) seek to answer frequently asked questions about diagnostic considerations and the approach to management by reviewing therapeutic options – a truly valuable clinical piece to guide any young gastroenterologist.
Our medical ethics series features a poignant piece written by Diana Anderson (University of California, San Francisco) and David Seres (Columbia University) on the role of nutritional support in patients with restrictive eating disorders. The article addresses the complex interplay between certain diagnoses and our emotive response as clinicians – a critical piece of patient care that is seldom discussed. The authors implore us to consider this difficult question: Could our unconscious partiality as physicians be worse than intentional harm?
Adjoa Anyane-Yeboa (Harvard University) discusses how her interest in health equity and health care policy led her to the Commonwealth Fund Fellowship in Minority Health Policy. Her passion for health care delivery reform and the care of vulnerable populations shines through as she describes how this post-GI fellowship pathway has been formative in shaping her career as a dynamic new gastroenterologist.
For those interested in serving as an expert witness, seasoned malpractice attorneys Daniel Mills and Courtney Lindbert (Cunningham, Meyer & Vedrine P.C.) offer a salient list of the “do’s and don’ts” of the medical expert. Finally, this summer’s DHPA Private Practice Perspectives article, written by Michael Weinstein (Capital Digestive Care), offers important considerations for evaluating independent GI practices and how their response to COVID-19 can dictate their preparedness for future crises.
If you have interest in contributing or have ideas for future TNG topics, please contact me ([email protected]), or Ryan Farrell ([email protected]), managing editor of TNG.
Stay well,
Vijaya L. Rao, MD
Editor-in-Chief
Assistant professor of medicine, University of Chicago, section of gastroenterology, hepatology & nutrition
Dear colleagues,
The August issue of The New Gastroenterologist has arrived! The summer of 2020 certainly looks different from years past, as the COVID-19 pandemic rages on and we continue to adjust to the new realities of our personal and professional lives. Our third-year fellows have graduated amidst these unusual circumstances, some facing an uncertain job landscape. Yet their hard work is not lost upon us – as we must step back to recognize their achievements and bid them congratulations on the culmination of several years of training.
The pandemic has been pervasive in medical education with a profound effect on our training programs. Two very resourceful fellows, Indira Bhavsar-Burke and Claire Jansson-Knodell (Indiana University), share their experience with COVID-19 and how they used this time to create an online curriculum for medical students who were pulled from their gastroenterology clinical rotations.
As we remain socially distanced, connecting through virtual platforms and social media seems more important than ever, but digital media can be difficult to navigate as physicians. Austin Chiang (Thomas Jefferson University) offers a candid snapshot of the benefits and pitfalls of social media as a gastroenterologist, with advice on how to optimize one’s professional presence online.
This quarter’s “In Focus” feature is an excellent, high-yield review of eosinophilic esophagitis. Ronak Vashi Patel and Ikuo Hirano (Northwestern University) seek to answer frequently asked questions about diagnostic considerations and the approach to management by reviewing therapeutic options – a truly valuable clinical piece to guide any young gastroenterologist.
Our medical ethics series features a poignant piece written by Diana Anderson (University of California, San Francisco) and David Seres (Columbia University) on the role of nutritional support in patients with restrictive eating disorders. The article addresses the complex interplay between certain diagnoses and our emotive response as clinicians – a critical piece of patient care that is seldom discussed. The authors implore us to consider this difficult question: Could our unconscious partiality as physicians be worse than intentional harm?
Adjoa Anyane-Yeboa (Harvard University) discusses how her interest in health equity and health care policy led her to the Commonwealth Fund Fellowship in Minority Health Policy. Her passion for health care delivery reform and the care of vulnerable populations shines through as she describes how this post-GI fellowship pathway has been formative in shaping her career as a dynamic new gastroenterologist.
For those interested in serving as an expert witness, seasoned malpractice attorneys Daniel Mills and Courtney Lindbert (Cunningham, Meyer & Vedrine P.C.) offer a salient list of the “do’s and don’ts” of the medical expert. Finally, this summer’s DHPA Private Practice Perspectives article, written by Michael Weinstein (Capital Digestive Care), offers important considerations for evaluating independent GI practices and how their response to COVID-19 can dictate their preparedness for future crises.
If you have interest in contributing or have ideas for future TNG topics, please contact me ([email protected]), or Ryan Farrell ([email protected]), managing editor of TNG.
Stay well,
Vijaya L. Rao, MD
Editor-in-Chief
Assistant professor of medicine, University of Chicago, section of gastroenterology, hepatology & nutrition
Database offers snapshot of common causes of pediatric allergic contact dermatitis
, according to an analysis of data from the Pediatric Allergic Contact Dermatitis Registry.
The registry is the first multicenter prospective database in the United States with a focus on pediatric allergic contact dermatitis. JiaDe (Jeff) Yu, MD, a dermatologist at Massachusetts General Hospital, Boston, was awarded a Dermatology Foundation Career Development Grant and formed the registry in 2018 “in an effort to gain a better understanding of allergic contact dermatitis in children,” Idy Tam, MS, said during the virtual annual meeting of the Society for Pediatric Dermatology. “There is currently limited data regarding the pediatric allergic contact dermatitis in the U.S., despite as many as 20% of children having allergic contact dermatitis.”
To date, the Pediatric Allergic Contact Dermatitis Registry consists of 10 academic medical centers with high volume pediatric patch testing across the United States: Massachusetts General Hospital, Boston; Brigham and Women’s Hospital, Boston; the University of Missouri–Columbia; Stanford (Calif.) University; the Medical University of South Carolina, Charleston; Texas Children’s Hospital, Houston; Northwestern University, Chicago; Emory University, Atlanta; Washington University, St. Louis; and the University of California, San Diego.
For the current analysis, Ms. Tam, a research fellow in the department of dermatology at Massachusetts General Hospital, and colleagues collected data on 218 patients under age 18 who were referred for an evaluation of allergic contact dermatitis at one of the 10 participating sites between January 2016 and June 2020.
The mean age of children at the time of their patch testing was 10 years, 62% were girls, and 66% had a history of atopic dermatitis (AD). Most (75%) were White, 14% were Black, 6% were Asian, the rest were from other racial backgrounds. The distribution of dermatitis varied; the top five most commonly affected sites were the face (62%), arms (35%), legs (29%), hands (27%), and neck (20%).
Ms. Tam reported that the mean number of allergens patch tested per child was 78. In all, 81% of children had one or more positive patch test reactions, with a similar rate among those with and without a history of AD (80% vs. 82%, respectively; P = .21). The five most common allergens were hydroperoxides of linalool (22%), nickel sulfate (19%), methylisothiazolinone (17%), cobalt chloride (13%), and fragrance mix I (12%).
The top two treatments at the time of patch testing were a topical corticosteroid (78%) and a topical calcineurin inhibitor (26%).
“This study has allowed for the increased collaboration among dermatologists with expertise in pediatric dermatology and allergic contact dermatitis,” concluded Ms. Tam, a fourth-year medical student at Tufts University, Boston. “We continue to actively seek further collaboration with a goal of creating the most comprehensive pediatric allergic contact dermatitis registry, which can improve our understanding of this condition in children and hopefully guide future research in this field.”
The work was recognized as one of the top poster abstracts at the meeting. The researchers reported having no relevant disclosures.
, according to an analysis of data from the Pediatric Allergic Contact Dermatitis Registry.
The registry is the first multicenter prospective database in the United States with a focus on pediatric allergic contact dermatitis. JiaDe (Jeff) Yu, MD, a dermatologist at Massachusetts General Hospital, Boston, was awarded a Dermatology Foundation Career Development Grant and formed the registry in 2018 “in an effort to gain a better understanding of allergic contact dermatitis in children,” Idy Tam, MS, said during the virtual annual meeting of the Society for Pediatric Dermatology. “There is currently limited data regarding the pediatric allergic contact dermatitis in the U.S., despite as many as 20% of children having allergic contact dermatitis.”
To date, the Pediatric Allergic Contact Dermatitis Registry consists of 10 academic medical centers with high volume pediatric patch testing across the United States: Massachusetts General Hospital, Boston; Brigham and Women’s Hospital, Boston; the University of Missouri–Columbia; Stanford (Calif.) University; the Medical University of South Carolina, Charleston; Texas Children’s Hospital, Houston; Northwestern University, Chicago; Emory University, Atlanta; Washington University, St. Louis; and the University of California, San Diego.
For the current analysis, Ms. Tam, a research fellow in the department of dermatology at Massachusetts General Hospital, and colleagues collected data on 218 patients under age 18 who were referred for an evaluation of allergic contact dermatitis at one of the 10 participating sites between January 2016 and June 2020.
The mean age of children at the time of their patch testing was 10 years, 62% were girls, and 66% had a history of atopic dermatitis (AD). Most (75%) were White, 14% were Black, 6% were Asian, the rest were from other racial backgrounds. The distribution of dermatitis varied; the top five most commonly affected sites were the face (62%), arms (35%), legs (29%), hands (27%), and neck (20%).
Ms. Tam reported that the mean number of allergens patch tested per child was 78. In all, 81% of children had one or more positive patch test reactions, with a similar rate among those with and without a history of AD (80% vs. 82%, respectively; P = .21). The five most common allergens were hydroperoxides of linalool (22%), nickel sulfate (19%), methylisothiazolinone (17%), cobalt chloride (13%), and fragrance mix I (12%).
The top two treatments at the time of patch testing were a topical corticosteroid (78%) and a topical calcineurin inhibitor (26%).
“This study has allowed for the increased collaboration among dermatologists with expertise in pediatric dermatology and allergic contact dermatitis,” concluded Ms. Tam, a fourth-year medical student at Tufts University, Boston. “We continue to actively seek further collaboration with a goal of creating the most comprehensive pediatric allergic contact dermatitis registry, which can improve our understanding of this condition in children and hopefully guide future research in this field.”
The work was recognized as one of the top poster abstracts at the meeting. The researchers reported having no relevant disclosures.
, according to an analysis of data from the Pediatric Allergic Contact Dermatitis Registry.
The registry is the first multicenter prospective database in the United States with a focus on pediatric allergic contact dermatitis. JiaDe (Jeff) Yu, MD, a dermatologist at Massachusetts General Hospital, Boston, was awarded a Dermatology Foundation Career Development Grant and formed the registry in 2018 “in an effort to gain a better understanding of allergic contact dermatitis in children,” Idy Tam, MS, said during the virtual annual meeting of the Society for Pediatric Dermatology. “There is currently limited data regarding the pediatric allergic contact dermatitis in the U.S., despite as many as 20% of children having allergic contact dermatitis.”
To date, the Pediatric Allergic Contact Dermatitis Registry consists of 10 academic medical centers with high volume pediatric patch testing across the United States: Massachusetts General Hospital, Boston; Brigham and Women’s Hospital, Boston; the University of Missouri–Columbia; Stanford (Calif.) University; the Medical University of South Carolina, Charleston; Texas Children’s Hospital, Houston; Northwestern University, Chicago; Emory University, Atlanta; Washington University, St. Louis; and the University of California, San Diego.
For the current analysis, Ms. Tam, a research fellow in the department of dermatology at Massachusetts General Hospital, and colleagues collected data on 218 patients under age 18 who were referred for an evaluation of allergic contact dermatitis at one of the 10 participating sites between January 2016 and June 2020.
The mean age of children at the time of their patch testing was 10 years, 62% were girls, and 66% had a history of atopic dermatitis (AD). Most (75%) were White, 14% were Black, 6% were Asian, the rest were from other racial backgrounds. The distribution of dermatitis varied; the top five most commonly affected sites were the face (62%), arms (35%), legs (29%), hands (27%), and neck (20%).
Ms. Tam reported that the mean number of allergens patch tested per child was 78. In all, 81% of children had one or more positive patch test reactions, with a similar rate among those with and without a history of AD (80% vs. 82%, respectively; P = .21). The five most common allergens were hydroperoxides of linalool (22%), nickel sulfate (19%), methylisothiazolinone (17%), cobalt chloride (13%), and fragrance mix I (12%).
The top two treatments at the time of patch testing were a topical corticosteroid (78%) and a topical calcineurin inhibitor (26%).
“This study has allowed for the increased collaboration among dermatologists with expertise in pediatric dermatology and allergic contact dermatitis,” concluded Ms. Tam, a fourth-year medical student at Tufts University, Boston. “We continue to actively seek further collaboration with a goal of creating the most comprehensive pediatric allergic contact dermatitis registry, which can improve our understanding of this condition in children and hopefully guide future research in this field.”
The work was recognized as one of the top poster abstracts at the meeting. The researchers reported having no relevant disclosures.
FROM SPD 2020
EMA gives green light to avapritinib for GIST, acalabrutinib for CLL
The CHMP recommended granting conditional marketing authorization for avapritinib (Ayvakit, Blueprint Medicines) for use in adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. About 6%-10% of GIST tumors harbor this mutation, and avapritinib is a selective and potent inhibitor of KIT and PDGFRA mutant kinases.
The CHMP also adopted a positive opinion for acalabrutinib (Calquence, AstraZeneca) for the treatment of chronic lymphocytic leukemia (CLL) as monotherapy in patients who are treatment-naive or have received at least one prior therapy.
The CHMP opinion on both drugs will be reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the EU.
Detailed recommendations for the use of both drugs will be provided in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the products receive marketing authorization by the European Commission.
First targeted therapy for mutation
If approved by the European Commission, avapritinib would be the first treatment in the EU indicated for patients with PDGFRA D842V-mutant GIST.
Avapritinib was approved by the US Food and Drug Administration (FDA) earlier this year for the aforementioned indication. The FDA approval was based on findings from the phase 1 NAVIGATOR trial, which included 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with the most common mutation, PDGFRA D842V.
For patients harboring a PDGFRA exon 18 mutation, the overall response rate (ORR) was 84%, with 7% having a complete response and 77% having a partial response. Patients with the PDGFRA D842V mutation achieved an ORR of 89%, with 8% having a complete response and 82% having a partial response.
“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies ... Today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a statement at the time of approval.
The most common side effects (≥ 20% of patients) observed in patients taking avapritinib include nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite, and memory impairment. There may also be a risk of intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued.
In the EU, conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required, the CHMP notes on its website.
Avapritinib had received an orphan medicine designation during development, which the EMA will review to determine if the designation can be maintained.
New treatment for CLL
Acalabrutinib is already approved in the United States, Canada, and Australia for the treatment of CLL and small lymphocytic lymphoma. The product was approved at the same time by all three regulatory authorities last year. In the United States, acalabrutinib had previously been approved for use in mantle cell lymphoma.
The CHMP’s positive opinion of acalabrutinib is based on results from two phase 3 trials, ELEVATE TN and ASCEND.
In the ASCEND trial, acalabrutinib was compared with investigator’s choice of idelalisib or bendamustine with rituximab. The trial, which involved 310 patients with relapsed/refractory CLL, showed that acalabrutinib improved progression-free survival (PFS).
At a median follow-up of 16.1 months, the median PFS was not reached with acalabrutinib and was 16.5 months with investigator’s choice of therapy (P < .0001).
The most commonly reported adverse events seen with acalabrutinib were respiratory tract infections, headache, bruising, contusion, diarrhea, nausea, rash, musculoskeletal pain, fatigue, decreased hemoglobin, and decreased platelets.
In the ELEVATE TN trial, acalabrutinib was given alone or combined with obinutuzumab and compared to chlorambucil plus obinutuzumab in patients with previously untreated CLL. There were 535 patients randomized to receive acalabrutinib alone (n = 179), acalabrutinib plus obinutuzumab (n = 179), and chlorambucil plus obinutuzumab (n = 177).
At a median follow-up of 28 months, the median PFS was not reached with acalabrutinib alone or with acalabrutinib plus obinutuzumab, but the median PFS was 22.6 months in the chlorambucil-obinutuzumab arm (P < .0001 for both comparisons).
The most common adverse events in the acalabrutinib arms were headache, diarrhea, neutropenia, and nausea.
A version of this article first appeared on Medscape.com.
The CHMP recommended granting conditional marketing authorization for avapritinib (Ayvakit, Blueprint Medicines) for use in adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. About 6%-10% of GIST tumors harbor this mutation, and avapritinib is a selective and potent inhibitor of KIT and PDGFRA mutant kinases.
The CHMP also adopted a positive opinion for acalabrutinib (Calquence, AstraZeneca) for the treatment of chronic lymphocytic leukemia (CLL) as monotherapy in patients who are treatment-naive or have received at least one prior therapy.
The CHMP opinion on both drugs will be reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the EU.
Detailed recommendations for the use of both drugs will be provided in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the products receive marketing authorization by the European Commission.
First targeted therapy for mutation
If approved by the European Commission, avapritinib would be the first treatment in the EU indicated for patients with PDGFRA D842V-mutant GIST.
Avapritinib was approved by the US Food and Drug Administration (FDA) earlier this year for the aforementioned indication. The FDA approval was based on findings from the phase 1 NAVIGATOR trial, which included 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with the most common mutation, PDGFRA D842V.
For patients harboring a PDGFRA exon 18 mutation, the overall response rate (ORR) was 84%, with 7% having a complete response and 77% having a partial response. Patients with the PDGFRA D842V mutation achieved an ORR of 89%, with 8% having a complete response and 82% having a partial response.
“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies ... Today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a statement at the time of approval.
The most common side effects (≥ 20% of patients) observed in patients taking avapritinib include nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite, and memory impairment. There may also be a risk of intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued.
In the EU, conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required, the CHMP notes on its website.
Avapritinib had received an orphan medicine designation during development, which the EMA will review to determine if the designation can be maintained.
New treatment for CLL
Acalabrutinib is already approved in the United States, Canada, and Australia for the treatment of CLL and small lymphocytic lymphoma. The product was approved at the same time by all three regulatory authorities last year. In the United States, acalabrutinib had previously been approved for use in mantle cell lymphoma.
The CHMP’s positive opinion of acalabrutinib is based on results from two phase 3 trials, ELEVATE TN and ASCEND.
In the ASCEND trial, acalabrutinib was compared with investigator’s choice of idelalisib or bendamustine with rituximab. The trial, which involved 310 patients with relapsed/refractory CLL, showed that acalabrutinib improved progression-free survival (PFS).
At a median follow-up of 16.1 months, the median PFS was not reached with acalabrutinib and was 16.5 months with investigator’s choice of therapy (P < .0001).
The most commonly reported adverse events seen with acalabrutinib were respiratory tract infections, headache, bruising, contusion, diarrhea, nausea, rash, musculoskeletal pain, fatigue, decreased hemoglobin, and decreased platelets.
In the ELEVATE TN trial, acalabrutinib was given alone or combined with obinutuzumab and compared to chlorambucil plus obinutuzumab in patients with previously untreated CLL. There were 535 patients randomized to receive acalabrutinib alone (n = 179), acalabrutinib plus obinutuzumab (n = 179), and chlorambucil plus obinutuzumab (n = 177).
At a median follow-up of 28 months, the median PFS was not reached with acalabrutinib alone or with acalabrutinib plus obinutuzumab, but the median PFS was 22.6 months in the chlorambucil-obinutuzumab arm (P < .0001 for both comparisons).
The most common adverse events in the acalabrutinib arms were headache, diarrhea, neutropenia, and nausea.
A version of this article first appeared on Medscape.com.
The CHMP recommended granting conditional marketing authorization for avapritinib (Ayvakit, Blueprint Medicines) for use in adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. About 6%-10% of GIST tumors harbor this mutation, and avapritinib is a selective and potent inhibitor of KIT and PDGFRA mutant kinases.
The CHMP also adopted a positive opinion for acalabrutinib (Calquence, AstraZeneca) for the treatment of chronic lymphocytic leukemia (CLL) as monotherapy in patients who are treatment-naive or have received at least one prior therapy.
The CHMP opinion on both drugs will be reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the EU.
Detailed recommendations for the use of both drugs will be provided in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the products receive marketing authorization by the European Commission.
First targeted therapy for mutation
If approved by the European Commission, avapritinib would be the first treatment in the EU indicated for patients with PDGFRA D842V-mutant GIST.
Avapritinib was approved by the US Food and Drug Administration (FDA) earlier this year for the aforementioned indication. The FDA approval was based on findings from the phase 1 NAVIGATOR trial, which included 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with the most common mutation, PDGFRA D842V.
For patients harboring a PDGFRA exon 18 mutation, the overall response rate (ORR) was 84%, with 7% having a complete response and 77% having a partial response. Patients with the PDGFRA D842V mutation achieved an ORR of 89%, with 8% having a complete response and 82% having a partial response.
“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies ... Today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a statement at the time of approval.
The most common side effects (≥ 20% of patients) observed in patients taking avapritinib include nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite, and memory impairment. There may also be a risk of intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued.
In the EU, conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required, the CHMP notes on its website.
Avapritinib had received an orphan medicine designation during development, which the EMA will review to determine if the designation can be maintained.
New treatment for CLL
Acalabrutinib is already approved in the United States, Canada, and Australia for the treatment of CLL and small lymphocytic lymphoma. The product was approved at the same time by all three regulatory authorities last year. In the United States, acalabrutinib had previously been approved for use in mantle cell lymphoma.
The CHMP’s positive opinion of acalabrutinib is based on results from two phase 3 trials, ELEVATE TN and ASCEND.
In the ASCEND trial, acalabrutinib was compared with investigator’s choice of idelalisib or bendamustine with rituximab. The trial, which involved 310 patients with relapsed/refractory CLL, showed that acalabrutinib improved progression-free survival (PFS).
At a median follow-up of 16.1 months, the median PFS was not reached with acalabrutinib and was 16.5 months with investigator’s choice of therapy (P < .0001).
The most commonly reported adverse events seen with acalabrutinib were respiratory tract infections, headache, bruising, contusion, diarrhea, nausea, rash, musculoskeletal pain, fatigue, decreased hemoglobin, and decreased platelets.
In the ELEVATE TN trial, acalabrutinib was given alone or combined with obinutuzumab and compared to chlorambucil plus obinutuzumab in patients with previously untreated CLL. There were 535 patients randomized to receive acalabrutinib alone (n = 179), acalabrutinib plus obinutuzumab (n = 179), and chlorambucil plus obinutuzumab (n = 177).
At a median follow-up of 28 months, the median PFS was not reached with acalabrutinib alone or with acalabrutinib plus obinutuzumab, but the median PFS was 22.6 months in the chlorambucil-obinutuzumab arm (P < .0001 for both comparisons).
The most common adverse events in the acalabrutinib arms were headache, diarrhea, neutropenia, and nausea.
A version of this article first appeared on Medscape.com.
Remdesivir Reduces Time to Recovery in Adults Hospitalized With COVID-19: A Meaningful Step in Therapeutic Discovery
Study Overview
Objective. To assess the clinical efficacy and safety of remdesivir in hospitalized adults with laboratory-confirmed COVID-19 and with evidence of lower respiratory tract involvement.
Design. Double-blinded, randomized, placebo-controlled, multicenter trial.
Setting and participants. Enrollment for the study took place between February 21, 2020, and April 19, 2020, at 60 trial sites and 13 subsites in the United States, Denmark, the United Kingdom, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore. Study participants included patients aged ≥ 18 years who were hospitalized and had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as determined by a positive reverse transcription polymerase chain reaction assay on a respiratory specimen. Participants had evidence of lower respiratory tract infection at the time of enrollment; this was defined as radiographic infiltrates by imaging study, peripheral oxygen saturation (SpO2) ≤ 94% on room air, or requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Exclusion criteria for study participation included abnormal liver enzymes (alanine aminotransferase, aspartate aminotransferase) more than 5 times the upper limit of normal range; impaired renal function or need for hemodialysis or hemofiltration; pregnancy or breastfeeding; or anticipated hospital discharge or transfer to another hospital within 72 hours of enrollment.
Intervention. Participants were randomized in a 1:1 ratio to the remdesivir group or the placebo group and were administered either intravenous infusions of remdesivir (200-mg loading dose on day 1, followed by a 100-mg maintenance dose daily on days 2 through 10, or until hospital discharge or death) or placebo for up to 10 days. Blinding was maintained by masking infusions with an opaque bag and tubing. Randomization was stratified by study site and disease severity at enrollment. Supportive care was delivered to all participants according to the standard of care at each trial site hospital. Clinical status, determined using an 8-category ordinal scale and the National Early Warning Score, was assessed daily for each participant while hospitalized (day 1 through day 29).
Blood samples for safety laboratory tests were collected, and oropharyngeal or nasopharyngeal swab testing was performed for viral RNA detection and quantification on days 1, 3, 5, 8, and 11. All serious adverse events (AEs) and grade 3/4 AEs that represented an increase in severity from day 1 and any grade 2 or higher suspected drug-related hypersensitivity reactions associated with the study drug or placebo administration were recorded.
Main outcome measures. The primary endpoint measure of this study was time to recovery, defined as the first day during the 28 days after enrollment on which a participant satisfied category 1 (ie, not hospitalized, no limitations of activities), 2 (ie, not hospitalized, limitation of activities, home oxygen requirement, or both), or 3 (ie, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; hospitalization was extended for infection-control reason) on the 8-category ordinal scale. Secondary outcomes included all-cause mortality at 14 and 28 days after enrollment and grade 3/4 AEs and serious AEs that occurred during trial participation. Analysis of the primary outcome was performed using a log-rank test of the time to recovery comparing remdesivir with placebo group, stratified by disease severity.
The study’s primary outcome was initially defined as a difference in clinical status as ascertained by the 8-category ordinal scale between groups of participants who were administered remdesivir versus placebo on day 15. Because of new knowledge gained external to the study about a more protracted COVID-19 clinical course than previously recognized, a change in primary outcome to time to recovery was proposed by trial statisticians, who were unaware of treatment assignments (72 participants had been enrolled) or outcome data (no interim data) on March 22, 2020, with subsequent amendment approval on April 2, 2020. On April 27, 2020, the Data and Safety Monitoring Board (DSMB) reviewed the interim study analysis (with data cutoff date of April 22, 2020) and recommended the report and mortality data to be provided to trial team members from the National Institute of Allergy and Infectious Diseases; these findings were subsequently made public.
Main results. A total of 1107 patients were assessed for eligibility, of whom 1063 underwent randomization, with 541 assigned to remdesivir and 522 to placebo. Results were unblinded early at the recommendation of DSMB due to findings from the interim analysis that showed reduced time to recovery in the group that received remdesivir. As of April 28, 2020, a total of 391 participants in the remdesivir group and 340 participants in the placebo group had completed the trial (day 29), recovered, or died. The mean age of participants was 58.9 ± 15.0 years, the majority were men (64.3%) and were White (53.2%), and the most common prespecified coexisting conditions were hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The vast majority of participants (88.7%) had severe COVID-19 disease at enrollment, defined as requiring invasive or noninvasive mechanical ventilation, requiring supplemental oxygen, SpO2 ≤ 94% on room air, or tachypnea (respiratory rate ≥ 24 breaths per minute).
Based on available data from 1059 participants (538 from the remdesivir group and 521 from the placebo group), those in the remdesivir group had a shorter median recovery time of 11 days (95% confidence interval [CI], 9-12) as compared to 15 days (95% CI, 13-19) in the placebo group, with a rate ratio for recovery of 1.32 (95% CI, 1.12-1.55; P < 0.001). Moreover, the odds of improvement on day 15 in the 8-category ordinal scale score were higher in the remdesivir group, compared to the placebo group (proportional odds model; odds ratio, 1.50; 95% CI, 1.18-1.91; P = 0.001; 844 participants).
Mortality rate by 14 days was numerically lower in the remdesivir group (7.1%) compared to the placebo group (11.9%), but the difference was not statistically significant (Kaplan-Meier, hazard ratio for death, 0.70; 95% CI, 0.47-1.04). Serious AEs were reported in 114 of the 541 (21.1%) participants in the remdesivir group and 141 of the 522 (27.0%) participants in the placebo group. Moreover, grade 3/4 AEs occurred in 156 (28.8%) participants in the remdesivir group and in 172 (33.0%) in the placebo group.
Conclusion. The study found that remdesivir, compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.
Commentary
Since the initial reporting of a cluster of cases of pneumonia in Wuhan, China, on December 31, 2019, SARS-CoV-2 has been identified as the cause of this new disease (COVID-19), and to-date SARS-CoV-2 infection has affected more than 15.2 million people globally, with more than 3.9 million cases in the United States alone.1 Despite an unprecedented global research effort, as well as public-private research partnerships, both in terms of scale and scope, an effective pharmacologic therapy for COVID-19 has so far eluded the scientific and medical community. Early trials of hydroxychloroquine and lopinavir-ritonavir did not demonstrate a clinical benefit in patients with COVID-19.2,3 Moreover, the first randomized controlled trial of remdesivir in COVID-19, a nucleoside analogue prodrug and a broad-spectrum antiviral agent previously shown to have inhibitory effects on pathogenic coronaviruses, was an underpowered study, and thus inconclusive.4 Thus, given the persistence of the COVID-19 pandemic and a current lack of effective vaccines or curative treatments, the study reported by Beigel and colleagues is timely and provides much needed knowledge in developing potential therapies for COVID-19.
The present report described the preliminary results of the first stage of the Adaptive Covid-19 Treatment Trial (ACCT-1), which aimed to evaluate the clinical efficacy and safety of intravenous remdesivir, as compared to placebo, in hospitalized adults with laboratory-confirmed COVID-19. The study itself was well-designed and conducted. The successful enrollment of more than 1000 participants randomized in a 1:1 ratio within a 2-month recruitment window, involving 60 international trial sites, shortly after the emergence of a new global pandemic was remarkable. This study provided the first evidence that remdesivir, an antiviral, can shorten time to recovery by approximately 31% compared to placebo in COVID-19 patients with lower respiratory tract involvement.
Interestingly, this beneficial effect of remdesivir on time to recovery was primarily observed in participants within the severe disease stratum (those requiring supplemental oxygen) at baseline (12 days in remdesivir group versus 18 days in placebo group), but not in those with mild-moderate disease at the time of study enrollment (5 days in either remdesivir or placebo group). Moreover, the beneficial effects of remdesivir on reducing time to recovery was not observed in participants who required mechanical ventilation or ECMO at enrollment. Thus, these preliminary results suggest that COVID-19 disease severity and timing, particularly in patients who require supplemental oxygen but prior to disease progression towards requiring mechanical ventilation, may present a window of opportunity to initiate remdesivir treatment in order to improve outcomes. Further analysis utilizing data from the entire cohort, including outcomes data from the full 28-day follow-up period, may better delineate the subgroup of hospitalized COVID-19 patients who may benefit most from remdesivir. Last, safety data from the present study, along with that reported by Wang and colleagues,4 provides evidence that intravenous remdesivir administration is likely safe in adults during the treatment period.
The preliminary results from the ACCT-1 provide early evidence that remdesivir shortens time to recovery in adult patients hospitalized for COVID-19 with pulmonary involvement. In light of these results, the US Food and Drug Administration issued an emergency use authorization for remdesivir on May 1, 2020, for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.5 In addition, remdesivir has also recently been approved as a therapy for COVID-19 in Japan, Taiwan, India, Singapore, and the United Arab Emirates, and has received conditional approval for use by the European Commission.6
Although these are encouraging developments in the race to identify effective therapeutics for COVID-19, a number of unanswered questions regarding the administration of remdesivir in the treatment of this disease remain. For instance, in an open-label, randomized, multicenter trial of patients with severe COVID-19 not requiring mechanical ventilation, treatment with a 5-day course versus a 10-day course of intravenous remdesivir did not result in a significant difference in efficacy.7 Thus, more studies are needed to better determine the shortest effective duration of remdesivir therapy in COVID-19 patients with different disease severity. Also, the mortality rate in COVID-19 patients who were treated with remdesivir remained high in the current study. Therefore, there is ample opportunity to evaluate treatment strategies, including multidrug interventions with remdesivir, to reduce mortality and improve clinical outcomes in patients hospitalized with COVID-19.
Applications for Clinical Practice
Remdesivir shortens time to recovery in adult patients hospitalized with COVID-19 who require supplemental oxygen therapy. While much needs to be learned in order to optimize treatment of COVID-19, preliminary findings from the current study provide an important first step towards these discoveries.
–Fred Ko, MD, MS
1. Johns Hopkins University Coronavirus Resource Center. https://coronavirus.jhu.edu/map.html. Accessed July 16, 2020.
2. Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial [published online April 14, 2020]. medRxiv 2020; doi:10.1101/2020.04.10.20060558.
3. Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe COVID-19. N Engl J Med. 2020;382:1787-1799.
4. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395:1569-1578.
5. Coronavirus (COVID-19) update: FDA issues Emergency Use Authorization for potential COVID-19 treatment. www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment. Accessed July 16, 2020.
6. Gilead’s COVID-19 antiviral remdesivir gets conditional EU clearance. www.reuters.com/article/us-health-coronavirus-eu-remdesivir/gileads-covid-19-antiviral-remdesivir-gets-conditional-eu-clearance-idUSKBN2441GK. Accessed July 6, 2020.
7. Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 days in patients with severe COVID-19. N Engl J Med. 2020 May 27.doi: 10.1056/NEJMoa2015301. Online ahead of print.
Study Overview
Objective. To assess the clinical efficacy and safety of remdesivir in hospitalized adults with laboratory-confirmed COVID-19 and with evidence of lower respiratory tract involvement.
Design. Double-blinded, randomized, placebo-controlled, multicenter trial.
Setting and participants. Enrollment for the study took place between February 21, 2020, and April 19, 2020, at 60 trial sites and 13 subsites in the United States, Denmark, the United Kingdom, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore. Study participants included patients aged ≥ 18 years who were hospitalized and had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as determined by a positive reverse transcription polymerase chain reaction assay on a respiratory specimen. Participants had evidence of lower respiratory tract infection at the time of enrollment; this was defined as radiographic infiltrates by imaging study, peripheral oxygen saturation (SpO2) ≤ 94% on room air, or requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Exclusion criteria for study participation included abnormal liver enzymes (alanine aminotransferase, aspartate aminotransferase) more than 5 times the upper limit of normal range; impaired renal function or need for hemodialysis or hemofiltration; pregnancy or breastfeeding; or anticipated hospital discharge or transfer to another hospital within 72 hours of enrollment.
Intervention. Participants were randomized in a 1:1 ratio to the remdesivir group or the placebo group and were administered either intravenous infusions of remdesivir (200-mg loading dose on day 1, followed by a 100-mg maintenance dose daily on days 2 through 10, or until hospital discharge or death) or placebo for up to 10 days. Blinding was maintained by masking infusions with an opaque bag and tubing. Randomization was stratified by study site and disease severity at enrollment. Supportive care was delivered to all participants according to the standard of care at each trial site hospital. Clinical status, determined using an 8-category ordinal scale and the National Early Warning Score, was assessed daily for each participant while hospitalized (day 1 through day 29).
Blood samples for safety laboratory tests were collected, and oropharyngeal or nasopharyngeal swab testing was performed for viral RNA detection and quantification on days 1, 3, 5, 8, and 11. All serious adverse events (AEs) and grade 3/4 AEs that represented an increase in severity from day 1 and any grade 2 or higher suspected drug-related hypersensitivity reactions associated with the study drug or placebo administration were recorded.
Main outcome measures. The primary endpoint measure of this study was time to recovery, defined as the first day during the 28 days after enrollment on which a participant satisfied category 1 (ie, not hospitalized, no limitations of activities), 2 (ie, not hospitalized, limitation of activities, home oxygen requirement, or both), or 3 (ie, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; hospitalization was extended for infection-control reason) on the 8-category ordinal scale. Secondary outcomes included all-cause mortality at 14 and 28 days after enrollment and grade 3/4 AEs and serious AEs that occurred during trial participation. Analysis of the primary outcome was performed using a log-rank test of the time to recovery comparing remdesivir with placebo group, stratified by disease severity.
The study’s primary outcome was initially defined as a difference in clinical status as ascertained by the 8-category ordinal scale between groups of participants who were administered remdesivir versus placebo on day 15. Because of new knowledge gained external to the study about a more protracted COVID-19 clinical course than previously recognized, a change in primary outcome to time to recovery was proposed by trial statisticians, who were unaware of treatment assignments (72 participants had been enrolled) or outcome data (no interim data) on March 22, 2020, with subsequent amendment approval on April 2, 2020. On April 27, 2020, the Data and Safety Monitoring Board (DSMB) reviewed the interim study analysis (with data cutoff date of April 22, 2020) and recommended the report and mortality data to be provided to trial team members from the National Institute of Allergy and Infectious Diseases; these findings were subsequently made public.
Main results. A total of 1107 patients were assessed for eligibility, of whom 1063 underwent randomization, with 541 assigned to remdesivir and 522 to placebo. Results were unblinded early at the recommendation of DSMB due to findings from the interim analysis that showed reduced time to recovery in the group that received remdesivir. As of April 28, 2020, a total of 391 participants in the remdesivir group and 340 participants in the placebo group had completed the trial (day 29), recovered, or died. The mean age of participants was 58.9 ± 15.0 years, the majority were men (64.3%) and were White (53.2%), and the most common prespecified coexisting conditions were hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The vast majority of participants (88.7%) had severe COVID-19 disease at enrollment, defined as requiring invasive or noninvasive mechanical ventilation, requiring supplemental oxygen, SpO2 ≤ 94% on room air, or tachypnea (respiratory rate ≥ 24 breaths per minute).
Based on available data from 1059 participants (538 from the remdesivir group and 521 from the placebo group), those in the remdesivir group had a shorter median recovery time of 11 days (95% confidence interval [CI], 9-12) as compared to 15 days (95% CI, 13-19) in the placebo group, with a rate ratio for recovery of 1.32 (95% CI, 1.12-1.55; P < 0.001). Moreover, the odds of improvement on day 15 in the 8-category ordinal scale score were higher in the remdesivir group, compared to the placebo group (proportional odds model; odds ratio, 1.50; 95% CI, 1.18-1.91; P = 0.001; 844 participants).
Mortality rate by 14 days was numerically lower in the remdesivir group (7.1%) compared to the placebo group (11.9%), but the difference was not statistically significant (Kaplan-Meier, hazard ratio for death, 0.70; 95% CI, 0.47-1.04). Serious AEs were reported in 114 of the 541 (21.1%) participants in the remdesivir group and 141 of the 522 (27.0%) participants in the placebo group. Moreover, grade 3/4 AEs occurred in 156 (28.8%) participants in the remdesivir group and in 172 (33.0%) in the placebo group.
Conclusion. The study found that remdesivir, compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.
Commentary
Since the initial reporting of a cluster of cases of pneumonia in Wuhan, China, on December 31, 2019, SARS-CoV-2 has been identified as the cause of this new disease (COVID-19), and to-date SARS-CoV-2 infection has affected more than 15.2 million people globally, with more than 3.9 million cases in the United States alone.1 Despite an unprecedented global research effort, as well as public-private research partnerships, both in terms of scale and scope, an effective pharmacologic therapy for COVID-19 has so far eluded the scientific and medical community. Early trials of hydroxychloroquine and lopinavir-ritonavir did not demonstrate a clinical benefit in patients with COVID-19.2,3 Moreover, the first randomized controlled trial of remdesivir in COVID-19, a nucleoside analogue prodrug and a broad-spectrum antiviral agent previously shown to have inhibitory effects on pathogenic coronaviruses, was an underpowered study, and thus inconclusive.4 Thus, given the persistence of the COVID-19 pandemic and a current lack of effective vaccines or curative treatments, the study reported by Beigel and colleagues is timely and provides much needed knowledge in developing potential therapies for COVID-19.
The present report described the preliminary results of the first stage of the Adaptive Covid-19 Treatment Trial (ACCT-1), which aimed to evaluate the clinical efficacy and safety of intravenous remdesivir, as compared to placebo, in hospitalized adults with laboratory-confirmed COVID-19. The study itself was well-designed and conducted. The successful enrollment of more than 1000 participants randomized in a 1:1 ratio within a 2-month recruitment window, involving 60 international trial sites, shortly after the emergence of a new global pandemic was remarkable. This study provided the first evidence that remdesivir, an antiviral, can shorten time to recovery by approximately 31% compared to placebo in COVID-19 patients with lower respiratory tract involvement.
Interestingly, this beneficial effect of remdesivir on time to recovery was primarily observed in participants within the severe disease stratum (those requiring supplemental oxygen) at baseline (12 days in remdesivir group versus 18 days in placebo group), but not in those with mild-moderate disease at the time of study enrollment (5 days in either remdesivir or placebo group). Moreover, the beneficial effects of remdesivir on reducing time to recovery was not observed in participants who required mechanical ventilation or ECMO at enrollment. Thus, these preliminary results suggest that COVID-19 disease severity and timing, particularly in patients who require supplemental oxygen but prior to disease progression towards requiring mechanical ventilation, may present a window of opportunity to initiate remdesivir treatment in order to improve outcomes. Further analysis utilizing data from the entire cohort, including outcomes data from the full 28-day follow-up period, may better delineate the subgroup of hospitalized COVID-19 patients who may benefit most from remdesivir. Last, safety data from the present study, along with that reported by Wang and colleagues,4 provides evidence that intravenous remdesivir administration is likely safe in adults during the treatment period.
The preliminary results from the ACCT-1 provide early evidence that remdesivir shortens time to recovery in adult patients hospitalized for COVID-19 with pulmonary involvement. In light of these results, the US Food and Drug Administration issued an emergency use authorization for remdesivir on May 1, 2020, for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.5 In addition, remdesivir has also recently been approved as a therapy for COVID-19 in Japan, Taiwan, India, Singapore, and the United Arab Emirates, and has received conditional approval for use by the European Commission.6
Although these are encouraging developments in the race to identify effective therapeutics for COVID-19, a number of unanswered questions regarding the administration of remdesivir in the treatment of this disease remain. For instance, in an open-label, randomized, multicenter trial of patients with severe COVID-19 not requiring mechanical ventilation, treatment with a 5-day course versus a 10-day course of intravenous remdesivir did not result in a significant difference in efficacy.7 Thus, more studies are needed to better determine the shortest effective duration of remdesivir therapy in COVID-19 patients with different disease severity. Also, the mortality rate in COVID-19 patients who were treated with remdesivir remained high in the current study. Therefore, there is ample opportunity to evaluate treatment strategies, including multidrug interventions with remdesivir, to reduce mortality and improve clinical outcomes in patients hospitalized with COVID-19.
Applications for Clinical Practice
Remdesivir shortens time to recovery in adult patients hospitalized with COVID-19 who require supplemental oxygen therapy. While much needs to be learned in order to optimize treatment of COVID-19, preliminary findings from the current study provide an important first step towards these discoveries.
–Fred Ko, MD, MS
Study Overview
Objective. To assess the clinical efficacy and safety of remdesivir in hospitalized adults with laboratory-confirmed COVID-19 and with evidence of lower respiratory tract involvement.
Design. Double-blinded, randomized, placebo-controlled, multicenter trial.
Setting and participants. Enrollment for the study took place between February 21, 2020, and April 19, 2020, at 60 trial sites and 13 subsites in the United States, Denmark, the United Kingdom, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore. Study participants included patients aged ≥ 18 years who were hospitalized and had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as determined by a positive reverse transcription polymerase chain reaction assay on a respiratory specimen. Participants had evidence of lower respiratory tract infection at the time of enrollment; this was defined as radiographic infiltrates by imaging study, peripheral oxygen saturation (SpO2) ≤ 94% on room air, or requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Exclusion criteria for study participation included abnormal liver enzymes (alanine aminotransferase, aspartate aminotransferase) more than 5 times the upper limit of normal range; impaired renal function or need for hemodialysis or hemofiltration; pregnancy or breastfeeding; or anticipated hospital discharge or transfer to another hospital within 72 hours of enrollment.
Intervention. Participants were randomized in a 1:1 ratio to the remdesivir group or the placebo group and were administered either intravenous infusions of remdesivir (200-mg loading dose on day 1, followed by a 100-mg maintenance dose daily on days 2 through 10, or until hospital discharge or death) or placebo for up to 10 days. Blinding was maintained by masking infusions with an opaque bag and tubing. Randomization was stratified by study site and disease severity at enrollment. Supportive care was delivered to all participants according to the standard of care at each trial site hospital. Clinical status, determined using an 8-category ordinal scale and the National Early Warning Score, was assessed daily for each participant while hospitalized (day 1 through day 29).
Blood samples for safety laboratory tests were collected, and oropharyngeal or nasopharyngeal swab testing was performed for viral RNA detection and quantification on days 1, 3, 5, 8, and 11. All serious adverse events (AEs) and grade 3/4 AEs that represented an increase in severity from day 1 and any grade 2 or higher suspected drug-related hypersensitivity reactions associated with the study drug or placebo administration were recorded.
Main outcome measures. The primary endpoint measure of this study was time to recovery, defined as the first day during the 28 days after enrollment on which a participant satisfied category 1 (ie, not hospitalized, no limitations of activities), 2 (ie, not hospitalized, limitation of activities, home oxygen requirement, or both), or 3 (ie, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; hospitalization was extended for infection-control reason) on the 8-category ordinal scale. Secondary outcomes included all-cause mortality at 14 and 28 days after enrollment and grade 3/4 AEs and serious AEs that occurred during trial participation. Analysis of the primary outcome was performed using a log-rank test of the time to recovery comparing remdesivir with placebo group, stratified by disease severity.
The study’s primary outcome was initially defined as a difference in clinical status as ascertained by the 8-category ordinal scale between groups of participants who were administered remdesivir versus placebo on day 15. Because of new knowledge gained external to the study about a more protracted COVID-19 clinical course than previously recognized, a change in primary outcome to time to recovery was proposed by trial statisticians, who were unaware of treatment assignments (72 participants had been enrolled) or outcome data (no interim data) on March 22, 2020, with subsequent amendment approval on April 2, 2020. On April 27, 2020, the Data and Safety Monitoring Board (DSMB) reviewed the interim study analysis (with data cutoff date of April 22, 2020) and recommended the report and mortality data to be provided to trial team members from the National Institute of Allergy and Infectious Diseases; these findings were subsequently made public.
Main results. A total of 1107 patients were assessed for eligibility, of whom 1063 underwent randomization, with 541 assigned to remdesivir and 522 to placebo. Results were unblinded early at the recommendation of DSMB due to findings from the interim analysis that showed reduced time to recovery in the group that received remdesivir. As of April 28, 2020, a total of 391 participants in the remdesivir group and 340 participants in the placebo group had completed the trial (day 29), recovered, or died. The mean age of participants was 58.9 ± 15.0 years, the majority were men (64.3%) and were White (53.2%), and the most common prespecified coexisting conditions were hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The vast majority of participants (88.7%) had severe COVID-19 disease at enrollment, defined as requiring invasive or noninvasive mechanical ventilation, requiring supplemental oxygen, SpO2 ≤ 94% on room air, or tachypnea (respiratory rate ≥ 24 breaths per minute).
Based on available data from 1059 participants (538 from the remdesivir group and 521 from the placebo group), those in the remdesivir group had a shorter median recovery time of 11 days (95% confidence interval [CI], 9-12) as compared to 15 days (95% CI, 13-19) in the placebo group, with a rate ratio for recovery of 1.32 (95% CI, 1.12-1.55; P < 0.001). Moreover, the odds of improvement on day 15 in the 8-category ordinal scale score were higher in the remdesivir group, compared to the placebo group (proportional odds model; odds ratio, 1.50; 95% CI, 1.18-1.91; P = 0.001; 844 participants).
Mortality rate by 14 days was numerically lower in the remdesivir group (7.1%) compared to the placebo group (11.9%), but the difference was not statistically significant (Kaplan-Meier, hazard ratio for death, 0.70; 95% CI, 0.47-1.04). Serious AEs were reported in 114 of the 541 (21.1%) participants in the remdesivir group and 141 of the 522 (27.0%) participants in the placebo group. Moreover, grade 3/4 AEs occurred in 156 (28.8%) participants in the remdesivir group and in 172 (33.0%) in the placebo group.
Conclusion. The study found that remdesivir, compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.
Commentary
Since the initial reporting of a cluster of cases of pneumonia in Wuhan, China, on December 31, 2019, SARS-CoV-2 has been identified as the cause of this new disease (COVID-19), and to-date SARS-CoV-2 infection has affected more than 15.2 million people globally, with more than 3.9 million cases in the United States alone.1 Despite an unprecedented global research effort, as well as public-private research partnerships, both in terms of scale and scope, an effective pharmacologic therapy for COVID-19 has so far eluded the scientific and medical community. Early trials of hydroxychloroquine and lopinavir-ritonavir did not demonstrate a clinical benefit in patients with COVID-19.2,3 Moreover, the first randomized controlled trial of remdesivir in COVID-19, a nucleoside analogue prodrug and a broad-spectrum antiviral agent previously shown to have inhibitory effects on pathogenic coronaviruses, was an underpowered study, and thus inconclusive.4 Thus, given the persistence of the COVID-19 pandemic and a current lack of effective vaccines or curative treatments, the study reported by Beigel and colleagues is timely and provides much needed knowledge in developing potential therapies for COVID-19.
The present report described the preliminary results of the first stage of the Adaptive Covid-19 Treatment Trial (ACCT-1), which aimed to evaluate the clinical efficacy and safety of intravenous remdesivir, as compared to placebo, in hospitalized adults with laboratory-confirmed COVID-19. The study itself was well-designed and conducted. The successful enrollment of more than 1000 participants randomized in a 1:1 ratio within a 2-month recruitment window, involving 60 international trial sites, shortly after the emergence of a new global pandemic was remarkable. This study provided the first evidence that remdesivir, an antiviral, can shorten time to recovery by approximately 31% compared to placebo in COVID-19 patients with lower respiratory tract involvement.
Interestingly, this beneficial effect of remdesivir on time to recovery was primarily observed in participants within the severe disease stratum (those requiring supplemental oxygen) at baseline (12 days in remdesivir group versus 18 days in placebo group), but not in those with mild-moderate disease at the time of study enrollment (5 days in either remdesivir or placebo group). Moreover, the beneficial effects of remdesivir on reducing time to recovery was not observed in participants who required mechanical ventilation or ECMO at enrollment. Thus, these preliminary results suggest that COVID-19 disease severity and timing, particularly in patients who require supplemental oxygen but prior to disease progression towards requiring mechanical ventilation, may present a window of opportunity to initiate remdesivir treatment in order to improve outcomes. Further analysis utilizing data from the entire cohort, including outcomes data from the full 28-day follow-up period, may better delineate the subgroup of hospitalized COVID-19 patients who may benefit most from remdesivir. Last, safety data from the present study, along with that reported by Wang and colleagues,4 provides evidence that intravenous remdesivir administration is likely safe in adults during the treatment period.
The preliminary results from the ACCT-1 provide early evidence that remdesivir shortens time to recovery in adult patients hospitalized for COVID-19 with pulmonary involvement. In light of these results, the US Food and Drug Administration issued an emergency use authorization for remdesivir on May 1, 2020, for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.5 In addition, remdesivir has also recently been approved as a therapy for COVID-19 in Japan, Taiwan, India, Singapore, and the United Arab Emirates, and has received conditional approval for use by the European Commission.6
Although these are encouraging developments in the race to identify effective therapeutics for COVID-19, a number of unanswered questions regarding the administration of remdesivir in the treatment of this disease remain. For instance, in an open-label, randomized, multicenter trial of patients with severe COVID-19 not requiring mechanical ventilation, treatment with a 5-day course versus a 10-day course of intravenous remdesivir did not result in a significant difference in efficacy.7 Thus, more studies are needed to better determine the shortest effective duration of remdesivir therapy in COVID-19 patients with different disease severity. Also, the mortality rate in COVID-19 patients who were treated with remdesivir remained high in the current study. Therefore, there is ample opportunity to evaluate treatment strategies, including multidrug interventions with remdesivir, to reduce mortality and improve clinical outcomes in patients hospitalized with COVID-19.
Applications for Clinical Practice
Remdesivir shortens time to recovery in adult patients hospitalized with COVID-19 who require supplemental oxygen therapy. While much needs to be learned in order to optimize treatment of COVID-19, preliminary findings from the current study provide an important first step towards these discoveries.
–Fred Ko, MD, MS
1. Johns Hopkins University Coronavirus Resource Center. https://coronavirus.jhu.edu/map.html. Accessed July 16, 2020.
2. Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial [published online April 14, 2020]. medRxiv 2020; doi:10.1101/2020.04.10.20060558.
3. Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe COVID-19. N Engl J Med. 2020;382:1787-1799.
4. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395:1569-1578.
5. Coronavirus (COVID-19) update: FDA issues Emergency Use Authorization for potential COVID-19 treatment. www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment. Accessed July 16, 2020.
6. Gilead’s COVID-19 antiviral remdesivir gets conditional EU clearance. www.reuters.com/article/us-health-coronavirus-eu-remdesivir/gileads-covid-19-antiviral-remdesivir-gets-conditional-eu-clearance-idUSKBN2441GK. Accessed July 6, 2020.
7. Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 days in patients with severe COVID-19. N Engl J Med. 2020 May 27.doi: 10.1056/NEJMoa2015301. Online ahead of print.
1. Johns Hopkins University Coronavirus Resource Center. https://coronavirus.jhu.edu/map.html. Accessed July 16, 2020.
2. Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial [published online April 14, 2020]. medRxiv 2020; doi:10.1101/2020.04.10.20060558.
3. Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe COVID-19. N Engl J Med. 2020;382:1787-1799.
4. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395:1569-1578.
5. Coronavirus (COVID-19) update: FDA issues Emergency Use Authorization for potential COVID-19 treatment. www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment. Accessed July 16, 2020.
6. Gilead’s COVID-19 antiviral remdesivir gets conditional EU clearance. www.reuters.com/article/us-health-coronavirus-eu-remdesivir/gileads-covid-19-antiviral-remdesivir-gets-conditional-eu-clearance-idUSKBN2441GK. Accessed July 6, 2020.
7. Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 days in patients with severe COVID-19. N Engl J Med. 2020 May 27.doi: 10.1056/NEJMoa2015301. Online ahead of print.
FDA okays new CAR T therapy, first for mantle cell lymphoma
The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.
“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”
In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”
The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).
In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response.
Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.
In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.
Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.
“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”
In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”
The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).
In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response.
Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.
In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.
Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.
“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”
In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”
The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).
In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response.
Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.
In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.
Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.
A version of this article originally appeared on Medscape.com.
US News releases latest top hospitals list, adds COVID heroes
This year’s rankings include special recognition of the “herculean efforts” by the nation’s healthcare professionals in fighting COVID-19, often at great personal risk.
“The US News Hospital Heroes series is a cornerstone of this year’s rankings package, profiling more than 65 health care heroes from across the country, along with commentary from top executives at hospitals who faced the pandemic head on,” a news release from the magazine explains.
“The pandemic has altered, perhaps permanently, how patients get care and from whom they get it. Amid the disruption, we are steadfastly committed to providing the public with authoritative data for comparing hospital quality,” Ben Harder, managing editor and chief of health analysis at US News, said in the release.
“No hospital’s clinical team came through this unprecedented health crisis unscathed. Our Hospital Heroes series is a tribute to recognizing individuals at urban and rural hospitals in communities across the country who have gone above and beyond during this unparalleled time in history,” said Harder.
Mayo Clinic Still Number One
Following Mayo Clinic, Cleveland Clinic in Ohio takes the number two spot this year (up from number four last year) in the magazine’s annual honor roll, which highlights hospitals that deliver “exceptional treatment across multiple areas of care.”
Johns Hopkins Hospital in Baltimore, Maryland, holds the number three spot, while New York-Presbyterian Hospital–Columbia and Cornell in New York City and UCLA Medical Center, Los Angeles, tie for the number four spot.
Massachusetts General Hospital in Boston, which held the number two spot last year, has fallen to number six. Rounding out the top 10, in order, are Cedars-Sinai Medical Center, Los Angeles; UCSF Medical Center, San Francisco; NYU Langone Hospitals, New York City; Northwestern Memorial Hospital, Chicago, Illinois.
2020–2021 Best Hospitals Honor Roll
1. Mayo Clinic, Rochester, Minnesota
2. Cleveland Clinic, Ohio
3. Johns Hopkins Hospital, Baltimore, Maryland
4. (tie) New York–Presbyterian Hospital–Columbia and Cornell, New York City
4. (tie) UCLA Medical Center, Los Angeles
6. Massachusetts General Hospital, Boston
7. Cedars-Sinai Medical Center, San Francisco
8. UCSF Medical Center, San Francisco
9. NYU Langone Hospitals, New York, New York City
10. Northwestern Memorial Hospital, Chicago
11. University of Michigan Hospitals–Michigan Medicine, Ann Arbor
12. Brigham and Women’s Hospital, Boston
13. Stanford Health Care–Stanford Hospital, Palo Alto, California
14. Mount Sinai Hospital, New York City
15. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia
16. Mayo Clinic–Phoenix
17. Rush University Medical Center, Chicago
18. (tie) Barnes-Jewish Hospital, Saint Louis
18. (tie) Keck Hospital of USC, Los Angeles
20. Houston Methodist Hospital, Texas
In the 2020–2021 Best Hospitals: Specialty Rankings, University of Texas MD Anderson Cancer Center continues to hold the number one spot in cancer, the Hospital for Special Surgery is number one in orthopedics, and the Cleveland Clinic is number one in cardiology and heart surgery.
For this year’s rankings, US News developed a new cardiac rating that measures the quality of hospitals› transcatheter aortic valve replacement, which is rapidly being adopted as a minimally invasive alternative to aortic valve surgery.
Top Five for Cancer
1. University of Texas MD Anderson Cancer Center, Houston
2. Memorial Sloan Kettering Cancer Center, New York City
3. Mayo Clinic, Rochester, Minnesota
4. Johns Hopkins Hospital, Baltimore, Maryland
5. Cleveland Clinic, Ohio
Top Five for Cardiology and Heart Surgery
1. Cleveland Clinic, Ohio
2. Mayo Clinic, Rochester, Minnesota
3. Cedars-Sinai Medical Center, Los Angeles
4. New York–Presbyterian Hospital–Columbia and Cornell, NYC
5. Massachusetts General Hospital, Boston
Top Five for Orthopedics
1. Hospital for Special Surgery, New York City
2. Mayo Clinic, Rochester, Minnesota
3. Cedars-Sinai Medical Center, Los Angeles
4. NYU Langone Orthopedic Hospital, New York City
5. Rush University Medical Center, Chicago
For the 2020–2021 rankings and ratings, US News compared more than 4500 medical centers across the country in 16 specialties and 10 procedures and conditions. Of these, 563 were recognized as Best Regional Hospitals on the basis of their strong performance in multiple areas of care. The top 20 hospitals, which deliver exceptional treatment across many areas of care, were also named to the honor roll.
The magazine notes that data for the 2020–2021 Best Hospitals rankings and ratings come from a period predating the COVID-19 pandemic and were not affected by the pandemic’s impact on hospitals. The methodologies are based largely on objective measures, such as risk-adjusted survival and discharge-to-home rates, volume, and quality of nursing, among other care-related indicators.
The full report on hospital ranking is available online.
This article first appeared on Medscape.com.
This year’s rankings include special recognition of the “herculean efforts” by the nation’s healthcare professionals in fighting COVID-19, often at great personal risk.
“The US News Hospital Heroes series is a cornerstone of this year’s rankings package, profiling more than 65 health care heroes from across the country, along with commentary from top executives at hospitals who faced the pandemic head on,” a news release from the magazine explains.
“The pandemic has altered, perhaps permanently, how patients get care and from whom they get it. Amid the disruption, we are steadfastly committed to providing the public with authoritative data for comparing hospital quality,” Ben Harder, managing editor and chief of health analysis at US News, said in the release.
“No hospital’s clinical team came through this unprecedented health crisis unscathed. Our Hospital Heroes series is a tribute to recognizing individuals at urban and rural hospitals in communities across the country who have gone above and beyond during this unparalleled time in history,” said Harder.
Mayo Clinic Still Number One
Following Mayo Clinic, Cleveland Clinic in Ohio takes the number two spot this year (up from number four last year) in the magazine’s annual honor roll, which highlights hospitals that deliver “exceptional treatment across multiple areas of care.”
Johns Hopkins Hospital in Baltimore, Maryland, holds the number three spot, while New York-Presbyterian Hospital–Columbia and Cornell in New York City and UCLA Medical Center, Los Angeles, tie for the number four spot.
Massachusetts General Hospital in Boston, which held the number two spot last year, has fallen to number six. Rounding out the top 10, in order, are Cedars-Sinai Medical Center, Los Angeles; UCSF Medical Center, San Francisco; NYU Langone Hospitals, New York City; Northwestern Memorial Hospital, Chicago, Illinois.
2020–2021 Best Hospitals Honor Roll
1. Mayo Clinic, Rochester, Minnesota
2. Cleveland Clinic, Ohio
3. Johns Hopkins Hospital, Baltimore, Maryland
4. (tie) New York–Presbyterian Hospital–Columbia and Cornell, New York City
4. (tie) UCLA Medical Center, Los Angeles
6. Massachusetts General Hospital, Boston
7. Cedars-Sinai Medical Center, San Francisco
8. UCSF Medical Center, San Francisco
9. NYU Langone Hospitals, New York, New York City
10. Northwestern Memorial Hospital, Chicago
11. University of Michigan Hospitals–Michigan Medicine, Ann Arbor
12. Brigham and Women’s Hospital, Boston
13. Stanford Health Care–Stanford Hospital, Palo Alto, California
14. Mount Sinai Hospital, New York City
15. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia
16. Mayo Clinic–Phoenix
17. Rush University Medical Center, Chicago
18. (tie) Barnes-Jewish Hospital, Saint Louis
18. (tie) Keck Hospital of USC, Los Angeles
20. Houston Methodist Hospital, Texas
In the 2020–2021 Best Hospitals: Specialty Rankings, University of Texas MD Anderson Cancer Center continues to hold the number one spot in cancer, the Hospital for Special Surgery is number one in orthopedics, and the Cleveland Clinic is number one in cardiology and heart surgery.
For this year’s rankings, US News developed a new cardiac rating that measures the quality of hospitals› transcatheter aortic valve replacement, which is rapidly being adopted as a minimally invasive alternative to aortic valve surgery.
Top Five for Cancer
1. University of Texas MD Anderson Cancer Center, Houston
2. Memorial Sloan Kettering Cancer Center, New York City
3. Mayo Clinic, Rochester, Minnesota
4. Johns Hopkins Hospital, Baltimore, Maryland
5. Cleveland Clinic, Ohio
Top Five for Cardiology and Heart Surgery
1. Cleveland Clinic, Ohio
2. Mayo Clinic, Rochester, Minnesota
3. Cedars-Sinai Medical Center, Los Angeles
4. New York–Presbyterian Hospital–Columbia and Cornell, NYC
5. Massachusetts General Hospital, Boston
Top Five for Orthopedics
1. Hospital for Special Surgery, New York City
2. Mayo Clinic, Rochester, Minnesota
3. Cedars-Sinai Medical Center, Los Angeles
4. NYU Langone Orthopedic Hospital, New York City
5. Rush University Medical Center, Chicago
For the 2020–2021 rankings and ratings, US News compared more than 4500 medical centers across the country in 16 specialties and 10 procedures and conditions. Of these, 563 were recognized as Best Regional Hospitals on the basis of their strong performance in multiple areas of care. The top 20 hospitals, which deliver exceptional treatment across many areas of care, were also named to the honor roll.
The magazine notes that data for the 2020–2021 Best Hospitals rankings and ratings come from a period predating the COVID-19 pandemic and were not affected by the pandemic’s impact on hospitals. The methodologies are based largely on objective measures, such as risk-adjusted survival and discharge-to-home rates, volume, and quality of nursing, among other care-related indicators.
The full report on hospital ranking is available online.
This article first appeared on Medscape.com.
This year’s rankings include special recognition of the “herculean efforts” by the nation’s healthcare professionals in fighting COVID-19, often at great personal risk.
“The US News Hospital Heroes series is a cornerstone of this year’s rankings package, profiling more than 65 health care heroes from across the country, along with commentary from top executives at hospitals who faced the pandemic head on,” a news release from the magazine explains.
“The pandemic has altered, perhaps permanently, how patients get care and from whom they get it. Amid the disruption, we are steadfastly committed to providing the public with authoritative data for comparing hospital quality,” Ben Harder, managing editor and chief of health analysis at US News, said in the release.
“No hospital’s clinical team came through this unprecedented health crisis unscathed. Our Hospital Heroes series is a tribute to recognizing individuals at urban and rural hospitals in communities across the country who have gone above and beyond during this unparalleled time in history,” said Harder.
Mayo Clinic Still Number One
Following Mayo Clinic, Cleveland Clinic in Ohio takes the number two spot this year (up from number four last year) in the magazine’s annual honor roll, which highlights hospitals that deliver “exceptional treatment across multiple areas of care.”
Johns Hopkins Hospital in Baltimore, Maryland, holds the number three spot, while New York-Presbyterian Hospital–Columbia and Cornell in New York City and UCLA Medical Center, Los Angeles, tie for the number four spot.
Massachusetts General Hospital in Boston, which held the number two spot last year, has fallen to number six. Rounding out the top 10, in order, are Cedars-Sinai Medical Center, Los Angeles; UCSF Medical Center, San Francisco; NYU Langone Hospitals, New York City; Northwestern Memorial Hospital, Chicago, Illinois.
2020–2021 Best Hospitals Honor Roll
1. Mayo Clinic, Rochester, Minnesota
2. Cleveland Clinic, Ohio
3. Johns Hopkins Hospital, Baltimore, Maryland
4. (tie) New York–Presbyterian Hospital–Columbia and Cornell, New York City
4. (tie) UCLA Medical Center, Los Angeles
6. Massachusetts General Hospital, Boston
7. Cedars-Sinai Medical Center, San Francisco
8. UCSF Medical Center, San Francisco
9. NYU Langone Hospitals, New York, New York City
10. Northwestern Memorial Hospital, Chicago
11. University of Michigan Hospitals–Michigan Medicine, Ann Arbor
12. Brigham and Women’s Hospital, Boston
13. Stanford Health Care–Stanford Hospital, Palo Alto, California
14. Mount Sinai Hospital, New York City
15. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia
16. Mayo Clinic–Phoenix
17. Rush University Medical Center, Chicago
18. (tie) Barnes-Jewish Hospital, Saint Louis
18. (tie) Keck Hospital of USC, Los Angeles
20. Houston Methodist Hospital, Texas
In the 2020–2021 Best Hospitals: Specialty Rankings, University of Texas MD Anderson Cancer Center continues to hold the number one spot in cancer, the Hospital for Special Surgery is number one in orthopedics, and the Cleveland Clinic is number one in cardiology and heart surgery.
For this year’s rankings, US News developed a new cardiac rating that measures the quality of hospitals› transcatheter aortic valve replacement, which is rapidly being adopted as a minimally invasive alternative to aortic valve surgery.
Top Five for Cancer
1. University of Texas MD Anderson Cancer Center, Houston
2. Memorial Sloan Kettering Cancer Center, New York City
3. Mayo Clinic, Rochester, Minnesota
4. Johns Hopkins Hospital, Baltimore, Maryland
5. Cleveland Clinic, Ohio
Top Five for Cardiology and Heart Surgery
1. Cleveland Clinic, Ohio
2. Mayo Clinic, Rochester, Minnesota
3. Cedars-Sinai Medical Center, Los Angeles
4. New York–Presbyterian Hospital–Columbia and Cornell, NYC
5. Massachusetts General Hospital, Boston
Top Five for Orthopedics
1. Hospital for Special Surgery, New York City
2. Mayo Clinic, Rochester, Minnesota
3. Cedars-Sinai Medical Center, Los Angeles
4. NYU Langone Orthopedic Hospital, New York City
5. Rush University Medical Center, Chicago
For the 2020–2021 rankings and ratings, US News compared more than 4500 medical centers across the country in 16 specialties and 10 procedures and conditions. Of these, 563 were recognized as Best Regional Hospitals on the basis of their strong performance in multiple areas of care. The top 20 hospitals, which deliver exceptional treatment across many areas of care, were also named to the honor roll.
The magazine notes that data for the 2020–2021 Best Hospitals rankings and ratings come from a period predating the COVID-19 pandemic and were not affected by the pandemic’s impact on hospitals. The methodologies are based largely on objective measures, such as risk-adjusted survival and discharge-to-home rates, volume, and quality of nursing, among other care-related indicators.
The full report on hospital ranking is available online.
This article first appeared on Medscape.com.
Updated EULAR/ACR criteria identify more lupus patients
Use of the 2019 EULAR/ACR criteria for systemic lupus erythematosus identified an additional 17% of lupus patients in a cohort of 133 women with undifferentiated connective tissue disease.
Several studies have applied the 2019 EULAR/ACR criteria for systemic lupus erythematosus (SLE) to different patient populations, wrote Massimo Radin, MD, of S. Giovanni Bosco Hospital, Turin, Italy, and colleagues.
“However, it is unknown if the new classifications criteria for SLE might impact on the categorization of patients previously diagnosed with undifferentiated connective tissue disease (UCTD),” they said in a brief report published in Arthritis Care & Research.
In addition, “being classified or not as having SLE may pose clinical and logistic consequences, as patients with a diagnosis of ‘SLE’ might be followed up according to a specific local protocol and have in-label access to certain medications (such as biologics) or may be eligible for the participation in clinical trials,” they wrote.
The investigators applied the 2019 EULAR/ACR criteria to a cohort of 133 women with UCTD but no other diagnosis. The average age of the women was 38 years; the average disease duration was 10 years. Patients who scored 10 points or more on positive clinical and immunological domains at the start of the study were classified as SLE under the 2019 EULAR/ACR criteria.
Overall, 22 patients (17%) met the classification criteria for SLE at the time of their first pregnancy.
Compared with the other patients in the cohort who were not classified as SLE, patients classified as SLE under the 2019 EULAR/ACR criteria had significantly higher frequency of mucocutaneous manifestations (5% vs. 23%), arthritis (17% vs. 59%), isolated urine abnormalities (1% vs. 18%), and highly specific antibodies (15% vs. 50%).
In addition, patients who met the 2019 EULAR/ACR SLE criteria were significantly more likely to meet the ACR 1997 and SLICC criteria after an average follow-up of 9 years compared with the rest of the cohort (18.2% vs. 1.8%). Patients who met the 2019 EULAR/ACR criteria also had significantly shorter disease duration than that of the other patients in the UCTD cohort (8.23 years vs. 10.7 years) and were significantly more likely to develop preeclampsia during pregnancy (18% vs. 0%).
The findings were limited by several factors including the retrospective design of the study and possible lack of generalizability to male patients, the researchers noted.
The results support the need for improved classification criteria for UCTD, as early identification of specific conditions can help guide treatment and reduce the risk of more severe symptoms and complications, the authors said.
“When discriminating between conditions with a marked overlap, such as SLE and UCTD, the proposal of new classification criteria should balance specificity and sensitivity,” the researchers wrote. “When developing new classification criteria, one approach is to select patients and the control groups as representative as possible of the settings (the medical practices) in which these criteria will be used.”
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Radin M et al. Art
Use of the 2019 EULAR/ACR criteria for systemic lupus erythematosus identified an additional 17% of lupus patients in a cohort of 133 women with undifferentiated connective tissue disease.
Several studies have applied the 2019 EULAR/ACR criteria for systemic lupus erythematosus (SLE) to different patient populations, wrote Massimo Radin, MD, of S. Giovanni Bosco Hospital, Turin, Italy, and colleagues.
“However, it is unknown if the new classifications criteria for SLE might impact on the categorization of patients previously diagnosed with undifferentiated connective tissue disease (UCTD),” they said in a brief report published in Arthritis Care & Research.
In addition, “being classified or not as having SLE may pose clinical and logistic consequences, as patients with a diagnosis of ‘SLE’ might be followed up according to a specific local protocol and have in-label access to certain medications (such as biologics) or may be eligible for the participation in clinical trials,” they wrote.
The investigators applied the 2019 EULAR/ACR criteria to a cohort of 133 women with UCTD but no other diagnosis. The average age of the women was 38 years; the average disease duration was 10 years. Patients who scored 10 points or more on positive clinical and immunological domains at the start of the study were classified as SLE under the 2019 EULAR/ACR criteria.
Overall, 22 patients (17%) met the classification criteria for SLE at the time of their first pregnancy.
Compared with the other patients in the cohort who were not classified as SLE, patients classified as SLE under the 2019 EULAR/ACR criteria had significantly higher frequency of mucocutaneous manifestations (5% vs. 23%), arthritis (17% vs. 59%), isolated urine abnormalities (1% vs. 18%), and highly specific antibodies (15% vs. 50%).
In addition, patients who met the 2019 EULAR/ACR SLE criteria were significantly more likely to meet the ACR 1997 and SLICC criteria after an average follow-up of 9 years compared with the rest of the cohort (18.2% vs. 1.8%). Patients who met the 2019 EULAR/ACR criteria also had significantly shorter disease duration than that of the other patients in the UCTD cohort (8.23 years vs. 10.7 years) and were significantly more likely to develop preeclampsia during pregnancy (18% vs. 0%).
The findings were limited by several factors including the retrospective design of the study and possible lack of generalizability to male patients, the researchers noted.
The results support the need for improved classification criteria for UCTD, as early identification of specific conditions can help guide treatment and reduce the risk of more severe symptoms and complications, the authors said.
“When discriminating between conditions with a marked overlap, such as SLE and UCTD, the proposal of new classification criteria should balance specificity and sensitivity,” the researchers wrote. “When developing new classification criteria, one approach is to select patients and the control groups as representative as possible of the settings (the medical practices) in which these criteria will be used.”
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Radin M et al. Art
Use of the 2019 EULAR/ACR criteria for systemic lupus erythematosus identified an additional 17% of lupus patients in a cohort of 133 women with undifferentiated connective tissue disease.
Several studies have applied the 2019 EULAR/ACR criteria for systemic lupus erythematosus (SLE) to different patient populations, wrote Massimo Radin, MD, of S. Giovanni Bosco Hospital, Turin, Italy, and colleagues.
“However, it is unknown if the new classifications criteria for SLE might impact on the categorization of patients previously diagnosed with undifferentiated connective tissue disease (UCTD),” they said in a brief report published in Arthritis Care & Research.
In addition, “being classified or not as having SLE may pose clinical and logistic consequences, as patients with a diagnosis of ‘SLE’ might be followed up according to a specific local protocol and have in-label access to certain medications (such as biologics) or may be eligible for the participation in clinical trials,” they wrote.
The investigators applied the 2019 EULAR/ACR criteria to a cohort of 133 women with UCTD but no other diagnosis. The average age of the women was 38 years; the average disease duration was 10 years. Patients who scored 10 points or more on positive clinical and immunological domains at the start of the study were classified as SLE under the 2019 EULAR/ACR criteria.
Overall, 22 patients (17%) met the classification criteria for SLE at the time of their first pregnancy.
Compared with the other patients in the cohort who were not classified as SLE, patients classified as SLE under the 2019 EULAR/ACR criteria had significantly higher frequency of mucocutaneous manifestations (5% vs. 23%), arthritis (17% vs. 59%), isolated urine abnormalities (1% vs. 18%), and highly specific antibodies (15% vs. 50%).
In addition, patients who met the 2019 EULAR/ACR SLE criteria were significantly more likely to meet the ACR 1997 and SLICC criteria after an average follow-up of 9 years compared with the rest of the cohort (18.2% vs. 1.8%). Patients who met the 2019 EULAR/ACR criteria also had significantly shorter disease duration than that of the other patients in the UCTD cohort (8.23 years vs. 10.7 years) and were significantly more likely to develop preeclampsia during pregnancy (18% vs. 0%).
The findings were limited by several factors including the retrospective design of the study and possible lack of generalizability to male patients, the researchers noted.
The results support the need for improved classification criteria for UCTD, as early identification of specific conditions can help guide treatment and reduce the risk of more severe symptoms and complications, the authors said.
“When discriminating between conditions with a marked overlap, such as SLE and UCTD, the proposal of new classification criteria should balance specificity and sensitivity,” the researchers wrote. “When developing new classification criteria, one approach is to select patients and the control groups as representative as possible of the settings (the medical practices) in which these criteria will be used.”
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Radin M et al. Art
FROM ARTHRITIS CARE & RESEARCH